major European markets

Transcription

Gen 27-02-15 Pg.1_Gen 18/11/05 Pg. 1 25/02/2015 18:33 Page 1
27 February 2015
COMPANY NEWS
2
Cipla gains ground in
2
North Africa via JVs
Actavis intends to adopt Allergan name 3
Teva plans to set up a biologicals facility 4
Wockhardt resolves faults at US factory 5
Sawai sees turnover rise
6
faster than profit
Aurobindo venture to target PCV vaccines 7
Growth in US helps Zydus to advance 8
Lannett turns gaze to Western Europe 9
Russia and Ukraine hit Richter’s results 10
Protopic rival peps Perrigo’s turnover 11
Towa cuts its costs to improve margins 12
Siegfried sorts out FDA Hameln letter 13
Glenmark grows its sales as profits slide 14
MARKET NEWS
15
FDA reopens debate on label change rule15
France must address declining sales trend 16
Canada will require
17
shortage notification
Input is invited over US interchangeability 19
OGD sets target for ANDA action dates 20
PRODUCT NEWS
21
Lupin enlists Celon for American Advair 21
Mylan must wait for
22
esomeprazole in US
Hospira and Pfenex develop ranibizumab 23
Lupin wins appeal on US Trizivir patent 24
Pregabalin dispute will persist in the UK25
Spain’s Kern Pharma
26
introduces infliximab
Momenta is open to abatacept options 27
Norway enjoys steep infliximab price cut 29
FEATURES
Pfizer eyes two top spots
with Hospira acquisition
32
32
REGULARS
Pipeline Watch – Remicade
28
Events – Our regular listing
30
Price Watch UK – UK pricing trends 31
People – Bayer’s Brandicourt
34
leads Sanofi as CEO
Rivals to Remicade reach
major European markets
R
ivals to the Remicade (infliximab) monoclonal antibody marketed by Janssen and
Merck are now available throughout Europe after Celltrion and Hospira seized on
expiries of paediatric extensions to supplementary protection certificates (SPCs) during
February to enter the market (see pages 24 and 28).
On 25 February, Celltrion announced launches of its Remsima biosimilar through partners
such as Kern Pharma and Mundipharma (see page 26) in Austria, Belgium, Denmark, France,
Germany and Greece, as well as in Italy, Luxembourg, the Netherlands, Spain, Sweden and the
UK. The treatment for autoimmune diseases was now available in 31 countries, the firm noted.
Hospira has launched its Inflectra (infliximab) biosimilar monoclonal antibody in
several European markets, including Austria, Denmark, France, Germany, Greece, Italy,
Luxembourg, the Netherlands, Spain and Sweden. “Inflectra is now available in 24 European
countries,” noted the injectables specialist, which already markets infliximab in Central and
Eastern Europe, as well as in some smaller Western European markets.
In September 2013, the European Commission authorised Remsima and Inflectra for treating
inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis,
adult and paediatric Crohn’s disease, adult and paediatric ulcerative colitis and plaque psoriasis.
Global Remicade turnover ahead by 2.9% to US$6.87 billion last year reported by Janssen’s
parent group, Johnson & Johnson, included US$1.64 billion in non-US International markets.
On 17 March, the US Food and Drug Administration’s (FDA’s) Arthritis Advisory
Committee will hold a public meeting to discuss a biologics license application (BLA) that
has been submitted by Celltrion for its CT-P13 proposed rival to Remicade.
US patent 6,284,471 protecting Remicade until September 2018 has just been rejected
upon re-examination by the US Patent and Trademark Office (USPTO). The ‘471 patent –
which covers assays using anti-tumour necrosis factor (TNF) antibodies – was one of three
patents for which Celltrion sought a declaratory judgement of non-infringement last year.
However, the two parties settled the litigation on confidential terms.
G
Pfizer pays US$17bn for Hospira
P
fizer has agreed to pay around US$17 billion, including assumed debt, to acquire
injectables specialist Hospira. The US$90-per-share deal has been approved unanimously
by both firms’ boards and is scheduled to close during the second half of this year, subject to
antitrust clearance and approval by Hospira’s shareholders. The agreement – which represents
a 39% premium on Hospira’s closing price on 4 February, and around four-times Hospira’s
annual sales – includes a US$500 million break-up fee.
“Hospira’s business aligns well with our new commercial structure and is an excellent
strategic fit for our Global Established Pharmaceutical (GEP) business, which will benefit
from a significantly enhanced product portfolio in growing markets,” commented Pfizer’s
chairman and chief executive officer, Ian Read.
“The expanded portfolio of sterile injectable pharmaceuticals, composed of Hospira’s
broad generic sterile injectables product line, including acute-care and oncology injectables,
with a number of differentiated presentations, as well as its biosimilars portfolio, combined
with GEP’s branded sterile injectables, including anti-infectives, anti-inflammatories and
cytotoxics, will create a leading global sterile injectables business,” Pfizer maintained.
G
For details of the deal, turn to page 32.
Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33 Page 2
COMPANY NEWS
STRATEGIC ALLIANCES/THIRD-QUARTER RESULTS
Cipla gains ground in North Africa via JVs
C
ipla has broadened its presence in North Africa by agreeing to
establish joint ventures with the company’s existing partners in
Algeria and Morocco.
Through its UK subsidiary, Cipla EU, the Indian firm will hold a
40% stake in a venture it is creating with its Algerian partner, Biopharm,
and a 60% stake in a similar scheme it is establishing with Cooper
Pharma and The Pharmaceutical Institute, Cipla’s allies in Morocco.
Both ventures – which are subject to certain regulatory approvals –
will be used as a vehicle to market Cipla’s respiratory franchise in
the respective countries, and will include the companies supplying
funds to build local manufacturing facilities. The Indian firm is
expected to contribute US$6 million of a total US$15 million in
Algeria, while it will pour up to US$15 million into its scheme in
Morocco, where Cipla will also promote its neurology drugs.
Meanwhile, Cipla has agreed to acquire for Rs960 million
(US$15.4 million) a 60% stake in privately-owned Indian firm Jay
Precision Pharma, an existing supplier of Cipla’s respiratory devices.
Jay Precision – which boasts a manufacturing facility in Vasai,
Maharashtra – had sales of around Rs300 million in its financial year
ended 31 March 2014. Slated to close by the end of next month, the
transaction was aimed at “integrating the value chain and will serve
as a platform for the development of next-generation respiratory
devices”, Cipla said.
Indian sales increased by 14%
In Cipla’s financial third quarter ended 31 December 2014,
domestic sales rising by 14.2% to Rs12.0 billion helped overcome
single-digit turnover slips from exports of active pharmaceutical
ingredients (APIs) and finished-dose formulations as the Indian
company improved its sales by 6.5% to Rs27.7 billion (see Figure 1).
However, the Indian firm’s export sales could soon be bolstered
after Cipla announced that it had “gone live” in North America, and
had subsequently introduced its first ‘own-label’ products in the region
including doxycycline, meloxicam, topiramate and valaciclovir.
Moreover, Cipla has revealed that it will be supplying esomeprazole
active pharmaceutical ingredient (API) and finished-dose formulation
27 February 2015
Issue 226
Editor:
Deputy Editor:
Assistant Editor:
Business Reporter:
Production Controller:
Production Editor:
Director of Subscriptions:
Awards Manager:
Managing Director:
Aidan Fry
David Wallace
Liudmila Kotko
Dean Rudge
Debi Minal
Jenna Meredith
Val Davis
Natalie Cornwell
Mike Rice
Editorial enquiries: GENERICS bulletin,
4 Poplar Road, Dorridge, Solihull,
West Midlands B93 8DB, UK.
Website: www.Generics-bulletin.com
Tel: +44 (0)1564 777550 Fax: +44 (0)1564 777524
E-mail: info@Generics-bulletin.com
Advertising enquiries:
As above, or ads@Generics-bulletin.com
SUBSCRIPTIONS
Subscription rates are published at
www.Generics-bulletin.com/subscribe.
2 GENERICS bulletin
27 February 2015
Third-quarter sales*
(Rs millions)
Change
(%)
Proportion
of total (%)
Formulations
APIs
Exports
12,750
1,510
14,260
-6.2
-4.4
-6.1
46
5
52
India
11,990
+14.2
43
Other
1,410
–
5
Cipla
27,650
+6.5
100
* rounded to nearest Rs10 million
Figure 1: Breakdown of Cipla’s net sales in its financial third quarter ended 31
December 2014 (Source – Cipla)
to Teva, following the Israeli group’s recent nod for the first US
generic rival to AstraZeneca’s Nexium blockbuster (Generics bulletin,
6 February 2015, page 17).
Elsewhere, Cipla’s in-licensing agreement with Teva in South
Africa though its local Cipla Medpro affiliate for access to “65 new
molecules” (Generics bulletin, 17 October 2014, page 6) has received
clearance from the country’s Competition Commission. The Indian
firm has also just been awarded a US$189 million share in a Global
Fund antiretroviral tender (see page 27).
Meanwhile, the founder of the Serum Institute of India, Cyrus
Poonwalla, has revealed that the company and Cipla had held initial
merger talks following their agreement covering paediatric vaccines
in Europe that was struck late last year (Generics bulletin, 5
December 2014, page 6). “We [Serum Institute] could never go up
for sale,” he said, “but we could merge with a company, for example
Cipla…there is a small chance that could happen.”
“We first have to see if the initial partnership bears fruit,”
Poonwalla added. “If it moves in the right direction, maybe we will
take it to the next stage.”
A marginal increase in Cipla’s expenses was offset by the firm’s
6.5% sales rise, as its pre-tax profit rose by 8.3% to Rs4.28 billion. G
Individual subscriptions
An annual subscription comprises:
■ 20 Generics bulletin newsletters;
■ AND at least 46 weekly News@Genericsbulletin
electronic newsflashes containing the week’s top
news stories (currently delivered by email).
Choice of formats
The 20 Generics bulletin newsletters are available:
■ EITHER as the digital Generics bulletin-i for
online access by desktop, and tablet and smartphone.
Mobile devices can have Apple or Android
operating systems.
■ OR in traditional hard-copy print format,
delivered by airmail.
Corporate and multiple subscriptions
Global Site Licences are available to companies.
These provide in-house electronic access for staff to
Generics bulletin and News@Genericsbulletin.
Please ask for a quotation.
Discounted multiple subscriptions are available to
Generics bulletin-i at the same location.
Subscription enquiries:
Contact subscriptions@Generics-bulletin.com
Terms & Conditions: These can be viewed in full at
www.Generics-bulletin.com/subscribe.
No part of this publication may be copied, reproduced,
stored in a retrieval system, distributed or transmitted
by any means, including electronic, mechanical,
photocopying or recording, without the prior written
permission of the publisher, or under the terms and
conditions of a Global Site Licence or of a licence
issued by the Copyright Licensing Agency (CLA) in
London, UK, or rights bodies in other countries that
have reciprocal agreements with the CLA.
Neither may this publication be exported, distributed
or circulated by any means without the prior written
permission of the publisher.
While due care has been taken to ensure the accuracy
of information contained in this publication, the
publisher makes no claim that it is free of error and
disclaims any liability whatsoever for any decisions or
actions taken as a result of its contents.
© OTC Publications Ltd. All rights reserved.
Generics bulletin® is registered as a trademark in
the European Community.
ISSN 1742-0784.
Company registered in England No 2765878.
Printed by Warwick Printing Company Limited,
Leamington Spa CV31 1QD, UK.
COMPANY NEWS
BUSINESS STRATEGY/ANNUAL RESULTS
Claris rejects talk
of injectables sale
C
laris Lifesciences has quashed media speculation that it is
considering selling its generic sterile injectables business,
Claris Injectables.
Responding to an article that appeared in India’s Economic Times
newspaper on 12 February, Claris announced in a disclosure to the
Bombay Stock Exchange (BSE): “At present we are not negotiating
the sale of a stake in the injectables business, and the board of
directors of the company has neither considered nor taken any
decision in this regard.”
According to the Times’ article, as many as seven companies
– Cipla, Dr Reddy’s, Lupin, Pfizer, Sandoz, Sun and Zydus Cadila –
had shown some level of interest in acquiring Claris Injectables for
around Rs25-30 billion (US$402-US$482 million), with several
having submitted initial bids.
Operating three manufacturing facilities that have been approved
by various regulatory authorities – including from the US, UK and
Australia – at a site in Ahmedabad, India, Claris Injectables offers
a wide portfolio of injectables across multiple delivery systems. The
operation – which Claris created last year by transferring its specialty
injectables business to a subsidiary – also spans product development,
regulatory affairs and sales and marketing units.
Claris Injectables forms the bulk of Claris’ operations, after the
Indian group sold an 80% stake in its infusion business in India and
other emerging markets to Japanese players Otsuka and Mitsui two
years ago (Generics bulletin, 9 August 2013, page 10).
The Indian group said its injectables sales grew by “approximately”
62% to Rs4.06 billion last year. Including a contribution made by the
Indian firm’s minority stake in its infusion business, group turnover
reached Rs7.14 billion. Emerging markets accounted for half of that
total, the US 23%, and other regulated markets the remaining 27%.
Having filed nine abbreviated new drug applications (ANDAs)
during 2014, the injectables unit ended the year with 13 of its 37
filings approved, and 24 pending review. The unit – which generated
earnings before interest, tax, depreciation and amortisation (EBITDA)
of Rs1.49 billion last year – plans to file 18 ANDAs this year, in
line with its target “to have a total of 100 ANDAs in the US within
the next three years”.
G
INVESTIGATIONS
Teva reports likely corruption
T
eva has identified, following a voluntary global investigation
into its business practices, potential issues in “Russia, certain
Eastern European countries, certain Latin American countries and
other countries” that “likely constitute” violation of the US Foreign
Corrupt Practices Act (FCPA).
“In connection with our investigation, we have also become
aware that affiliates in certain countries provided to local authorities
inaccurate or altered information relating to marketing or promotional
practices,” the Israeli group admitted.
Noting that its investigation was expected to continue at least until
the end of the year, Teva stressed that it had “brought and continue
to bring these issues to the attention of the Securities and Exchange
Commission (SEC) and the US Department of Justice (DoJ)”. Any
fines or disgorged profits could be “material”, it acknowledged. G
Actavis intends to
adopt Allergan name
A
ctavis plans to adopt the Allergan name for its corporate identity
and branded portfolio once it completes its US$66 billion takeover
of the ophthalmics specialist in the next few weeks. However, the
group will retain the Actavis name “for select geographic regions and
product portfolios”. The change in corporate name is subject to
shareholder approval.
“By adopting the Allergan name for the corporation, we will
ensure that our corporate identity reflects the dramatic evolution of
our company,” explained president and chief executive officer Brent
Saunders. “For more than 65 years, the Allergan name has represented
innovation in branded pharmaceuticals.”
“The Actavis name has represented our global commitment to
leadership in generic, branded generic and OTC pharmaceuticals and
to increased access to more affordable prescription medicine,” he
continued. “Retaining the Actavis name reflects this heritage, as well
as the considerable equity of the Actavis name with our customers
in key markets around the world.”
Actavis – which has recently unveiled its senior management
team following the Allergan deal (see page 35) – increased its turnover
Business
segment
Annual sales
(US$ millions)
Change
(%)
Operating
margin (%)
North American Generics
International
Generics/International
4,174
2,574
6,747
+6.6
+2.8
+5.1
–
–
32.0
North American Brands
4,631
+335.9
20.0
ANDA Distribution
1,684
+40.7
4.7
Actavis
13,062
+50.5
–*
* operating loss of US$1.27 billion includes US$4.43 billion
of expenses not attributed to business segments
Figure 1: Breakdown of Cipla’s net sales in its financial third quarter ended 31
December 2014 (Source – Cipla)
last year by 50.5% to US$13.1 billion due to a full-year contribution
from Warner Chilcott and consolidating Forest from 1 July 2014.
International sales outside of North America grew by 2.8% to
US$2.57 billion, due to a US$123 million input from Forest’s nonUS brands and a contribution from Warner Chilcott that almost trebled
to US$181 million. Those factors were offset in part by a US$237
million decrease from the Western European commercial operations
that the group divested to Aurobindo on 1 April last year. At the same
time, Actavis closed its acquisition of Thai generics specialist Silom
(Generics bulletin, 18 April 2014, page 3).
“In our North American Generics business, strong results were
driven by continued performance of our generic versions of Lidoderm
(lidocaine) and Concerta (methylphenidate), and fourth-quarter launches
of generic versions of Intuniv (guanfacine) and Celebrex (celecoxib),”
Saunders stated. Sales rose by 6.6% to US$4.17 billion (see Figure 1).
North American Brands turnover reached US$4.63 billion, while
higher prices and volumes pushed up revenues by the group’s US
Anda Distribution business by 40.7% to US$1.68 billion.
Acquisition-related charges – including a US$190 million
goodwill write-off on the Pharmatech drug-delivery business that
Actavis has agreed to sell to investment firm TPG – caused the group
to post a US$1.27 billion operating loss.
G
27 February 2015
GENERICS bulletin 3
COMPANY NEWS
Teva plans to set up a biologicals facility
T
eva is developing a plan to establish a “significant” biologics
production facility, according to its chief executive officer, Erez
Vigodman. “That is one gap we have. And we will over time also craft
a plan to deal with go-to-market capability. We might then pursue a
partner to accelerate the pace of execution,” he told investors.
Operations chief Carlo De Notaristefani noted that the group’s
current mammalian and microbial manufacturing capacity was “at a
small scale”. “We need to expand that, and we are currently assessing
the best location to do this,” he revealed.
Commenting on Teva’s biosimilars strategy, Generics head Siggi
Olafsson admitted he would “love to have more” candidates in the
biosimilars second wave, comprising mainly monoclonal antibodies.
The first wave of growth hormones, epoetins and filgrastims were
generating annual sales of US$200-US$300 million for Teva, he noted.
“We need a little bit bigger pipeline in wave two to be a real
player in the 2020-2021 timeframe,” Olafsson recognised. “We are
looking for the right assets and partner to be a real player in the
market in five to six years.”
Options included acquisitions, joint ventures and co-development
deals, he explained. While more than 100 companies claimed to have
usable second-wave projects, he said Teva had limited that selection
to “probably five to 10 companies that really have strong assets”.
Teva’s combination of generics and specialty brands expertise
was a key commercial advantage, Olafsson maintained. “We do not
expect any interchangeability, at least in the first few years,” he said.
As an example of Teva’s ability to market biologics, he cited the firm’s
Granix (tbo-filgrastim) brand – authorised as a standalone biologic –
in the US, which had captured more than a 15% market share.
Olafsson said Teva was also expanding its presence in generic
injectables, especially in long-acting formulations. Having tackled
manufacturing issues in recent years, the company was “re-entering
the market” in the US, he said, with recent launches such as
enoxaparin and linezolid set to push up US injectables turnover from
“just over US$100 million” in 2014 to at least US$300 million this
year (Generics bulletin, 16 January 2015, page 29). Teva’s global
injectables turnover was around US$500-US$700 million he added.
Noting Pfizer’s US$17 billion planned takeover of Hospira,
Olafsson said Teva intended to be a niche US injectables player.
“We are not competing on the big-volume antibiotics and oncology
products,” he said. Rather, he added, Teva was focusing on hard-tomake injectables such as a version of Luitpold’s Venofer (iron sucrose).
A 6% sales rise to US$4.42 billion in US Generics sales last
year failed to compensate fully for declines in Teva’s Europe and
Rest of the World regions as its global Generics turnover dipped by
1% to US$9.81 billion (see Figure 1). In local currencies, global
sales – including sales of active pharmaceutical ingredients (APIs)
to third parties that stalled at US$724 million – edged up by 1%.
Exclusive or first-to-market launches of generic Xeloda
(capecitabine) and Lovaza (omega-3 ethyl esters) contributed to the
US gains, as did introducing a rival to Evista (raloxifene). Launching
injectable carboplatin and enoxaparin, as well as celecoxib capsules
and buprenorphine/naloxone sublingual tablets helped to maintain
fourth-quarter US Generics sales at US$1.18 billion. But declines
of 16% in Europe and of 12% in the Rest of the World – due in part
to exchange-rate shifts – reduced global Generics turnover by 8%
to US$2.47 billion in the fourth quarter.
Full-year Generics sales in Teva’s 36 European countries – the
European Union, Norway, Switzerland, Albania and the countries
of the former Yugoslavia – fell by 6% to US$3.15 billion. Teva said
the 7% local-currency decrease was “mainly due to our focus on
4 GENERICS bulletin
27 February 2015
Annual sales
(US$ millions)
Change
(%)
Proportion
of total (%)
US
Europe
Rest of the World
Generic Medicines
4,418
3,148
2,248
9,814
+6
-6
-5
-1
22
16
11
48
Copaxone/CNS
Oncology
Respiratory
Women’s Health
Others
Specialty Medicines
5,575
1,180
957
504
344
8,560
+1
+17
-1
-1
-5
+2
28
6
5
2
2
42
OTC/Other
1,898
-6
9
Teva
20,272
±0
100
Figure 1: Breakdown by business segment of Teva Pharmacetical Industries’
sales in 2014 (Source – Teva)
profitable business as well as market dynamics in certain countries
including Germany, France and Spain”.
Olafsson said Teva’s team in Germany was “doing extremely
well”. While local Generics sales were down by 13% last year on
“lower participation in the tender market and increasing pressure
on prices in the retail generics segment”, the team had successfully
launched several respiratory brands. French Generics sales fell by 12%
amid “increasing competition” and revised rules on pharmacy discounts.
“We really do not want to go too much into the tender business in
Spain,” Olafsson added. The firm said a 13% Generics slide in Spain
was “due mainly to the impact of the implementation of new
commercial policies, and the increasing scope of the tendering system
in the Andalucía region, in which we chose not to participate”.
Olafsson said “the UK did very well”, seizing on local supply
shortages to raise local sales by 1%. And “improvements in our supply
management” helped Italian sales to grow by 12%, while turnover
in Switzerland rose by 4% on higher volumes driven by recent launches.
A reported 5% Generics decline to US$2.25 billion in the group’s
Rest of the World region equated to 4% local-currency growth. In
Russia, a 14% slide translated to a 3% local-currency gain as higher
sales of branded generics outweighed lower revenues from government
tenders. Canadian sales rose by 5%, or by 12% in local-currency
terms, aided by reversing a pricing reserve. But “quality and supply
issues”, as well as price cuts imposed in April 2014, cut turnover in
Japan by a tenth, or by 3% in the local currency.
Higher sales in the US and Canada, as well as better margins
on third-party API sales, boosted Teva’s Generics gross margin by
2.1 percentage points to 43.3%. Research and development costs
rose by 5% to US$517 million, but sales and marketing expenses
fell by 18% to US$1.58 billion, due in part to lower royalty payments
on US sales of generic Pulmicort (budesonide). A 29% gain to US$2.15
billion in the Generics segment’s operating profit – excluding
unallocated corporate expenses – improved the segment’s operating
margin by 5.1 points to 21.9%.
The Israeli group’s overall performance followed a similar trend.
Operating profit more than doubled to US$3.95 billion following a
prior-year charge to settle damages for the firm’s at-risk US launch
of pantoprazole. But turnover stagnated at US$20.3 billion, as
Copaxone (glatiramer acetate) accounted for almost half of Specialty
Medicines sales ahead by 2% to US$8.56 billion.
G
COMPANY NEWS
MANUFACTURING
FDA warns Apotex
over Indian facility
F
ailing to ensure laboratory records include complete data, to
exercise appropriate controls over computer systems and to
establish and follow appropriate written procedures are among the
“serious current good manufacturing practice (cGMP) violations”
listed in a warning letter that the US Food and Drug Administration
(FDA) has issued to the Apotex Research Private Limited (ARPL)
finished-dose facility in Bommasandra near Bangalore, India.
“The FDA’s concern pertains to the practice of disregarding
failing results, conducting trial injections and retesting products
without any investigation,” the letter states. “We are also concerned
that you do not have documentation to support your decision to retest
samples of lots that had initially failed to meet specifications, and
you allowed manufacturing activities to occur without the oversight
of your quality unit.”
Noting that some of the deficiencies found during an inspection
of the ARPL site conducted in June and July last year were repeat
observations from a 2010 warning letter, the FDA tells Apotex to
provide “a comprehensive evaluation of the extent of the inaccuracy
of recorded and reported data” along with a risk assessment of the
effects of the observed failures and a management strategy for global
corrective and preventive action plans.
“The inspection of your facility documented multiple incidents
of performing ‘trial’ testing of samples, disregarding test results
and reporting only those results from additional tests conducted,”
the letter states. In particular, it accuses the firm of using only “the
most favourable result” from impurity testing, while quality-control
personnel “created unauthorised folders on laboratory
computerised systems with appropriate oversight”.
“ARPL’s inability to prevent and detect poor recordkeeping
practices raises serious concerns regarding the quality system in place
at the time of the inspection,” objects the FDA.
Pointing out that it had notified the firm of the agency’s concern
about trial injections during a January 2014 inspection of the
Apotex Pharmachem bulk-drugs unit at Bommasandra, the FDA
states: “Our findings during this inspection suggest that corrective
actions were not implemented globally.” As a result of that inspection,
the FDA issued a warning letter to Apotex Pharmachem midway
through last year (Generics bulletin, 11 July 2014, page 2), followed
by an import alert. In response, Health Canada asked Apotex to
quarantine products made at the ARPL plant (Generics bulletin, 3
October 2014, page 3).
At that time, Apotex insisted it was “absolutely confident in the
safety and effectiveness of all our products throughout the entirety
of our manufacturing and testing processes, regardless of where it
was manufactured”.
Meanwhile, the FDA has also issued a warning letter to Micro
Labs’ facility in Verna, India, following an inspection in May 2014.
The cGMP deficiencies listed include: failure to ensure that
laboratory records include complete data derived from necessary
testing; failure to exercise appropriate controls over computer
systems; and failure to record or justify deviations from required
laboratory-control mechanisms.
As in the Apotex warning letter, the FDA took issue with
unauthorised ‘trial’ high performance liquid chromatography (HPLC)
injections prior to injections used in reported test results. The agency
also pulled up the Indian company for filing field alert reports of
failed impurity results almost a month late.
G
MANUFACTURING/THIRD-QUARTER RESULTS
Wockhardt resolves
faults at US factory
W
ockhardt says it has “resolved all issues” at its Morton Grove
facility in Illinois, US, which last year led the US Food and
Drug Administration (FDA) to issue the Indian firm with ‘Form
483’ observations for deficiencies related to quality controls and
procedures (Generics bulletin, 5 September 2014, page 4).
“Our responses to the [Form] 483…have been found satisfactory
by the FDA and operations continue as normal,” the Indian firm’s
managing director, Murtaza Khorakiwala, told investors. “We
[appointed] a new leadership in quality function [six months ago],
and then we had a one-on-one meeting with the FDA,” he revealed.
“[The agency] wanted some more clarification, but they very clearly
indicated that they intend to take no further action.”
The firm’s Morton Grove facility has increased in importance
to Wockhardt since the FDA barred US imports from its Indian
Chikalthana and Waluj plants in 2013 (Generics bulletin, 6 December
2013, page 3). However, Khorakiwala revealed, Wockhardt had
invited the FDA to begin inspections of all its facilities. This
included Wockhardt’s newest facility in Shendra, India, from where
the company has filed the “majority” of its abbreviated new drug
applications (ANDAs) over the past two years.
Meanwhile, the UK’s Medicines and Healthcare products
Regulatory Agency (MHRA) has allowed Wockhardt to begin
importing products from Chikalthana to the UK again after it removed
a statement of non-compliance from the site.
The agency had only just extended that statement of non-compliance
to cover all drugs manufactured at Chikalthana (Generics bulletin,
6 February 2015, page 2), having two years ago issued the facility
with a restricted good manufacturing practice (GMP) certificate, to
avoid market shortages, following observations of critical
deficiencies (Generics bulletin, 18 October 2013, page 6).
In its financial third quarter ended 31 December 2014, a UK
sales boom offset depleted turnover in the US caused by those
manufacturing issues as Wockhardt’s sales rose by 12% to Rs13.8
billion (US$223 million). UK turnover more than doubled – increasing
by 141% to Rs6.30 billion – while sales in the US tumbled by 48%
to Rs2.82 billion (see Figure 1).
That UK turnover surge also comfortably offset sales dips of
16% to Rs330 million and 37% to Rs390 million in France and Ireland
respectively. But Wockhardt’s turnover in India and Emerging Markets
rose by almost a fifth to Rs3.86 billion, as the Indian firm launched
seven products in its domestic market during the quarter.
Despite ramping up research and development spending by more
than a fifth to Rs1.19 billion, Wockhardt’s pre-tax profit improved
by 29% to Rs4.08 billion.
G
Region
Third-quarter sales
(Rs millions*)
Change
(%)
Proportion
of total (%)
Europe
7,140
+92
52
India/Emerging
3,860
+18
28
US
2,820
-48
20
Wockhardt
13,820
+12
100
* rounded to the nearest Rs10 million
Figure 1: Breakdown by region of Wockhardt’s sales in its financial third quarter
ended 31 December 2014 (Source – Wockhardt)
27 February 2015
GENERICS bulletin 5
COMPANY NEWS
THIRD-QUARTER RESULTS
NINE-MONTH RESULTS
S
G
Sun’s sales stall on Sawai sees turnover
constraints in supply rise faster than profit
un Pharma blamed “temporary supply constraints arising from
remediation efforts” for its net sales stalling at Rs42.8 billion
(US$688 million) in the Indian group’s financial third quarter ended
31 December 2014. The company – which is awaiting Indian court
clearance to complete its US$4 billion takeover of Ranbaxy – posted
a 9% fall in pre-tax profit to Rs18.5 billion.
Managing director Dilip Shanghvi said he expected supplies from
the firm’s formulations facility in Halol, India, to improve as Sun
implemented corrective actions to deficiencies identified during an
inspection by the US Food and Drug Administration (FDA) in
September last year (Generics bulletin, 5 December 2014, page 3).
“We have given a detailed response, and we are meeting all the dates
that we shared with the FDA,” he told investors.
Shanghvi blamed “temporary supply constraints at Halol, the loss
of exclusivity for generic Prandin (repaglinide) and a significant
decline in doxycycline sales” for US Formulations turnover sliding
by 4.4% to Rs25.6 billion. The local-currency decline was 5% to
US$413 million, even though the group’s Taro affiliate – in which
Sun holds a 69% stake – posted an 11.3% sales rise to US$238 million,
despite “a volume decrease across all markets”.
“Temporary supply constraints arising from remediation efforts”
also contributed to Formulations turnover in Sun’s Rest of the World
region tumbling by 14.7% to Rs4.44 billion (see Figure 1). And
excluding Taro’s non-US sales, turnover in the region plunged by 29%.
But the US and Rest of the World declines were cancelled out by
the Indian group improving branded generics turnover in its domestic
market by 21.4% to Rs11.5 billion, aided by 15 product launches since
Third-quarter sales
(Rs millions)
Change
(%)
Proportion
of total (%)
US
India
Rest of the World
Formulations
25,602
11,500
4,444
41,546
-4.4
+21.4
-14.7
+0.2
60
27
10
97
Bulk Drugs
1,811
+4.0
4
Other/eliminations
-562
–
-1
42,795
-0.2
100
Sun Pharma
Figure 1: Breakdown by region and business of Sun Pharma’s gross sales in its
financial third quarter ended 31 December 2014 (Source – Sun Pharma)
April 2014. Bulk Drugs sales to third parties rose by 4.0% to Rs1.81
billion as Sun stepped up internal vertical integration for key products.
Supply constraints and increased compliance costs at Halol, as
well as integration planning ahead of the planned closure of the
Ranbaxy deal by the end of March, contributed to a 3% slide to
Rs19.1 billion in group earnings before interest, tax, depreciation
and amortisation (EBITDA).
Sun’s research and development spending reached Rs3.89 billion,
or just over 9% of sales, as the firm made “significant investments”
in clinical development of tildrakizumab, a psoriasis monoclonal
antibody recently licensed from Merck & Co.
Having submitted 19 abbreviated new drug applications (ANDAs)
between April and December 2014 – and received 14 approvals –
Sun ended the quarter with 358 approved ANDAs and 131 pending
FDA final clearance, including 11 tentative approvals.
G
6 GENERICS bulletin
27 February 2015
overnment initiatives to increase the use of generics were
credited by Sawai Pharmaceutical as the primary driver for its
sales increasing by 18.0% to ¥80.2 billion (US$669 million) in the
first nine months of its financial year ending 31 March 2015. But
during that period, the Japanese firm’s operating profit grew by just
2.4% to ¥17.4 billion, giving it an operating margin 3.3 percentage
points lower at 21.7%.
Recent price revisions – mandated by Japan’s National Health
Insurance (NHI) system – and “growing sales of low-priced products”
explained the disparity between the growth in sales and operating
profit, Sawai said. Volumes had increased by 26.9%, the company
observed, compared to the 18.0% value rise.
Cardiovascular drugs enjoyed a sales rise of just under a fifth
to ¥24.5 billion, or around 30% of Sawai’s turnover. The category
accounted for a quarter of Sawai’s sales by volume, as the number
of units sold advanced by a third. Meanwhile, volume rises of 42.5%
for blood products and 59.3% for respiratory drugs translated to value
rises of 34.8% to ¥9.13 billion and 46.6% to ¥2.27 billion respectively.
Sawai envisages annual sales ahead by 18.0% to ¥106 billion and
an operating profit that will grow by a tenth to ¥21.0 billion.
G
MERGERS & ACQUISITIONS/ANNUAL RESULTS
Valeant aims to acquire Salix
V
aleant has agreed to buy Salix Pharmaceuticals in deal that values
the US gastrointestinal specialist at US$14.5 billion. The US$158per-share cash transaction is scheduled to close during the second
quarter of this year.
“The growing gastrointestinal market has attractive fundamentals,
and Salix has a portfolio of terrific products that are outpacing the
market in terms of volume growth, [as well as] a promising near-term
pipeline of innovative products,” commented Valeant’s chairman and
chief executive officer, Michael Pearson.
Meanwhile, Valeant has just closed a US$400 million deal to buy
several assets of bankrupt Provenge (sipuleucel-T) provider Dendreon.
Last year, a full-year contribution from its Bausch & Lomb
acquisition lifted Valeant’s group turnover by 43% to US$8.26 billion.
The firm said this equated to 13% ‘same-store’ organic growth.
On the same basis, the group’s Emerging Markets sales rose by
8%. As Figure 1 shows, the reported increase was 42% to US$2.10
billion, as turnover in the firm’s Asia/Africa region more than doubled.
“We continued to see strong organic growth in several emerging markets
such as China, the Middle East and Russia,” Pearson stated.
G
Annual sales
(US$ millions)
Change
(%)
Proportion
of total (%)
Developed markets
6,167
+44
75
Europe/Middle East
Asia/Africa
Latin America
Emerging markets
1,087
574
435
2,096
+34
+110
+11
+42
13
7
5
25
Valeant
8,264
+43
100
Figure 1: Breakdown of Valeant’s sales in 2014 (Source – Valeant)
COMPANY NEWS
MERGERS & ACQUISITIONS
BUSINESS STRATEGY/THIRD-QUARTER RESULTS
J
A
Julphar buys stake in Aurobindo venture to
Bangladeshi partner target PCV vaccines
ulphar has established a direct presence in Bangladesh by acquiring a
majority stake in its local partner, RAK Pharmaceuticals, for US$9.5
million. The two firms, the group based in the United Arab Emirates
(UAE) pointed out, had held a “long-term strategic alliance” that
covered a technology-transfer and marketing deal for several products.
“RAK is a relatively young, fresh company with solid
infrastructure, growth rates and a healthy pipeline,” commented
Julphar’s chief executive officer, Ayman Sahli. The deal, he said,
would help the firm to serve 160 million people and a Bangladeshi
pharma market valued at around US$1.3 billion.
“The stable investment outlook and the growing healthcare needs
of a large, mostly underserved population make Bangladesh an
attactive market for investors,” Sahli added. “Healthcare plays a
major role in the expanding economy of Bangladesh, and with this
comes a clear need for increased manufacturing.”
A subsidiary of RAK Ceramics, RAK Pharma operates
production facilities 42 kilometres north of Dhaka, Bangladesh, on
a complex that includes a separate unit for cephalosporin antibiotics
in tablet, capsule and dry-syrup forms. Having started marketing
operations in mid-2009, the company has built up a broad portfolio
of more than 100 branded generics that in 2013 generated a turnover
of US$5.7 million, representing growth of 24%.
Having in 2012 invested US$150 million in a manufacturing
facility in the UAE dedicated to producing raw materials for insulins
and biosimilars, Julphar in 2013 launched its first international
finished-dose facility in Ethiopia with local partner Medtech,“initiating
a global expansion strategy to increase manufacturing capabilities
across its major markets”.
“We are in the early stages of expanding our manufacturing
capabilities in Ethiopia,” the group’s director of Sub-Saharan
Africa, Steve Gravenor, told Generics bulletin. “We plan to build a
new fill-and-finish facility which will produce insulin, using our own
active pharmaceutical ingredient (API) manufactured in the UAE.”
“Our short-term aim is to expand our manufacturing base in
Ethiopia, to supply domestic and eventually export markets. Further
abroad, Julphar is exploring partnerships with local players from
private and government sectors,” Gravenor explained, adding that
this strategy fitted well with the African Union Commission’s
Pharmaceutical Manufacturing Plan (PMP) to expand and improve
the quality and scale of pharmaceutical production in the continent.
Meanwhile, Julphar – which achieved a turnover of AED1.4
billion (US$381 million) last year – is constructing a facility in Jeddah,
Saudi Arabia, with local partner Cigalah Group.
G
IN BRIEF
STADA ARZNEIMITTEL said impairment charges of just over
C100 million (US$113 million) related to its businesses in the
Commonwealth of Independent States (CIS) and Eastern Europe
almost halved its 2014 net profit to C64.6 million, according to
preliminary annual results. Currency effects added a further C20.7
million burden. The German group expects to report annual group
turnover ahead by 3% to C2.06 billion, equivalent to a 1% rise once
adjusted for acquisitions and currency shifts. And this year, Stada
anticipates lower profits from Russia due to devaluation of the rouble
and “increased risks in connection with consumer mood”.
G
urobindo Pharma plans to set up a joint venture with Tergene
Biotech, an Indian company that is developing a pneumococcal
conjugate vaccine (PCV). “Aurobindo will hold a majority stake in
the joint venture and will fund the product development in a phased
manner spanning three years,” the Indian firm stated, adding that
the commercially-available PCV had “limited competition and a
global branded market of more than US$5 billion”.
“It will take around three years for us to get the development
completed and the facility up and running,” noted Aurobindo’s
managing director N Govindarajan. “Initially our focus will be on
tender markets.” “This is an area that is much tougher than typical
development projects,” he commented, highlighting limited competition.
Stronger Formulations sales, driven in part by having acquired
Actavis’ commercial operations in Western Europe, enabled Aurobindo
to raise its group turnover by 47.9% to Rs31.7 billion (US$513 million)
in its financial third quarter ended 31 December 2014. Formulations
turnover ahead by 76.2% to Rs25.3 billion more than offset a 9.4%
fall to Rs6.74 billion in sales of active pharmaceutical ingredients
(APIs) due to lower semi-synthetic and non-betalactam revenues.
Incorporating the former Actavis operations had strengthened
Business
segment
Third-quarter sales Change
(Rs millions)
(%)
Proportion
of total (%)
US
Europe
Rest of world
Antiretrovirals
Formulations
12,012
8,609
1,338
3,338
25,297
+29.0
+470.9
±0.0
+51.5
+76.2
38
27
4
11
80
Active Ingredients
6,744
-9.4
21
Eliminations/Others
-379
–
-1
31,662
+47.9
100
Aurobindo
Figure 1: Breakdown by business segment of Aurobindo Pharma’s sales in its
financial third quarter ended 31 December 2014 (Source – Aurobindo)
Aurobindo’s presence in Germany, the Netherlands, Portugal and
Spain, Govindarajan pointed out, while providing access to Belgium,
France and Italy. “The revenue and profit numbers for the integrated
European operations have been in line with our expectations,” he stated.
Aurobindo’s European Formulations sales showed an almost
six-fold rise to Rs8.61 billion, accounting for more than a quarter
of group turnover. Another 38% came from US Formulations turnover
rising by 29.0% to Rs12.0 billion (see Figure 1) on market-share
gains and “opportunistic price increases”.
The firm’s AuroMedics US injectables unit – which has 45 files
pending approval – contributed sales ahead by 71% to US$18 million.
Having incorporated its US$133 million purchase of nutraceuticals
company Natrol from 4 December, Aurobindo intends to expand
the business – which has annual sales of around US$100 million –
beyond the US (Generics bulletin, 5 December 2014, page 5).
Formulations sales in the Rest of the World region stalled at
Rs1.34 billion as the company switched focus in South Africa from
tenders to the private market. Antiretroviral Formulations turnover
climbed by 51.5% to Rs3.34 billion as the firm won “notable tenders”.
Higher raw-material and operating expenses caused the Indian
group’s pre-tax profit to slip by 2.0% to Rs5.39 billion.
G
27 February 2015
GENERICS bulletin 7
COMPANY NEWS
SECOND-QUARTER RESULTS
H
U
Pack pushes Aceto Growth in US helps
to single-digit rise Zydus to advance
uman Health sales rising by almost two-fifths to US$55.4 million
helped Aceto to increase its group sales by 6.2% to US$124
million in its financial second quarter ended 31 December 2014.
Higher selling, general and administrative expenses caused a slight
drop in pre-tax profit to US$10.5 million.
However, chief executive officer Sal Guccione commented,
Human Health turnover – which was driven by Aceto’s acquisition
of Pack Pharmaceuticals last year (Generics bulletin, 4 April 2014,
Business
segment
Second-quarter sales Change
Gross
(US$ millions)
(%) margin (%)
Human Health
Performance Chemicals
Pharmaceutical Ingredients
55.4
35.8
32.6
+39.2
-8.8
-13.1
29.5
18.9
21.3
Aceto
123.8
+6.2
24.3
Figure 1: Breakdown by business segment of Aceto’s sales and gross margin in
the financial second quarter ended 31 December 2014 (Source – Aceto)
page 3) – had been stung by a US$12.5 million impact from priceprotection adjustments associated with increases. “The benefit of [this]
should be realised later this fiscal year and in future periods,” he noted.
Those improved Human Health sales marginally overcame
Pharmaceutical Ingredients and Performance Chemicals dips (see
Figure 1), the former of which Guccione attributed to lower sales of
an undisclosed “high-margin” active pharmaceutical ingredient (API).
While the Aceto head insisted he was confident that Aceto’s
pipeline of 52 abbreviated new drug applications (ANDAs) – of
which 24 had been pending US Food and Drug Administration (FDA)
approval for more than two years – would further drive sales, he
acknowledged the industry was “seeing slowness” in FDA approvals.
Potential launches this year include paricalcitol soft-gel capsules
bought from Par last year as part of a US$8.2 million deal (Generics
bulletin, 19 September 2014, page 17).
G
MANUFACTURING/ANNUAL RESULTS
Biocad plans monoclonal site
R
ussia’s Biocad plans to invest more than RUB3.0 billion (US$48
million) into constructing a raw-materials plant for monoclonal
antibodies next to its existing operations in Saint Petersburg, Russia.
The company has started designing the project and expects commercial
production to begin by 2018.
According to the company’s founder and chief executive, Dmitriy
Morozov, the facility will help to meet “unforeseen demand” for the
firm’s monoclonal antibodies, especially for rituximab, for which
Biocad won a supply contract worth of RUB5.98 billion in a recent
Russian government tender (Generics bulletin, 3 November 2014,
page 19). He said the new plant would mainly produce oncology
and autoimmune monoclonal antibodies.
Meanwhile, last year, Biocad almost trebled its turnover to
RUB8.5 billion. With three upcoming oncology launches – including
bortezomib, bevacizumab and empegfilgrastim (Generics bulletin,
16 January 2015, page 22) – the Russian company expects to raise
its turnover by 30% to around RUB11.0 billion this year.
G
8 GENERICS bulletin
27 February 2015
S Formulations turnover that increased by 41.8%, coupled with
sales growth of more than a fifth in its Emerging Markets
region, helped Zydus Cadila to report group sales ahead by 17.4%
to Rs22.0 billion (US$353 million) in its financial third quarter
ended 31 December 2014.
With sales of Rs8.96 billion, US Formulations accounted for
just over two-fifths of the Indian group’s turnover, while Emerging
Markets added 5% with Rs1.01 billion. During the quarter, the
company filed five abbreviated new drug applications (ANDAs),
taking its total US submissions to 255.
Meanwhile, in India – where Zydus recently became “the first
company anywhere in the world” to launch biosimilar adalimumab
after introducing its Exemptia rival to AbbVie’s Humira blockbuster
(Generics bulletin, 16 January 2015, page 17) – sales rose by
more than a tenth to Rs8.46 billion, comfortably compensating for
double-digit sales dips in Europe and Latin America to Rs847 million
and Rs610 million respectively (see Figure 1).
Zydus – which halted operations in Japan a year ago (Generics
bulletin, 3 February 2014, page 3) – increased its turnover through
joint ventures and alliances by a fifth to Rs1.22 billion as active
pharmaceutical ingredient (API) sales stalled at Rs734 million.
The group’s pre-tax profit rose by more than half to Rs3.75
billion, aided by lower finance costs, as Zydus increased its research
and development investment by 52.7% to Rs1.88 billion.
G
Third-quarter sales
(Rs millions)
Change Proportion
(%)
of total (%)
India
8,464
+10.5
39
US
Europe
Latin America
Emerging Markets
APIs
Animal Health/others
Exports
8,959
847
610
1,013
734
136
12,298
+41.8
-28.6
-11.3
+22.5
+0.4
-16.5
+22.3
41
4
3
5
3
1
56
Joint ventures
1,217
+20.2
6
Zydus Cadila
21,979
+17.4
100
Figure 1: Breakdown by business and region of Zydus Cadila’s gross sales in its
financial third quarter ended 31 December 2014 (Source – Zydus Cadila)
DIVESTMENTS
Kabi divests its compounder
F
resenius Kabi has divested its German intravenous oncology
compounding business, CFL, for an undisclosed sum. The purchaser
is NewCo Pharma, a compounding company founded by pharmacist
Michael Schill.
Despite having sold Oberursel-based CFL, which generated a
turnover of C77 million (US$88 million) last year through a network
of centres spread through Germany, Kabi plans to remain active in
the compounding business. “In Germany,” the firm stated, “the focus
will be on parenteral nutrition products, an area that offers attractive
growth opportunities.”
G
COMPANY NEWS
ANNUAL RESULTS
Brazil bounces for
Generics at Sanofi
A
recovery in its Brazilian business enabled Sanofi’s Generics unit
to report sales that increased by 11.1% as reported, and by 16.2%
at constant exchange rates, to C1.81 billion (US$2.06 billion) last year.
Excluding Brazil, the unit suffered a 2.8% constant-currency decline.
Including Brazil, Generics sales in Emerging Markets advanced
by 38.8% on a constant-currency basis to C1.11 billion. That gain
more than outweighed sales slides of 4.3% to C533 in Western Europe
and 31.3% to C123 million in the US, as Generics turnover in Sanofi’s
Rest of the World region climbed by 27.8% to C43 million.
The Generics unit’s “very satisfactory recovery in Brazil” came
against a 2013 performance in which “challenges in Brazil” – resulting
from loading trade channels with “significantly and inappropriately
in excess of volumes needed to satisfy sell-out demand” – caused
global Generics turnover to fall by 11.9% to C1.63 billion (Generics
bulletin, 14 February 2014, page 2).
Brazilian turnover up by 22% to C71 million in the fourth
quarter of last year contributed to a 4.5% constant-currency Generics
gain in Emerging Markets to C291 million. But Sanofi’s total fourthquarter sales of Generics fell by 0.6% – and by 2.3% as reported –
to C467 million, reflecting declines of 7.7% to C133 million in
Western Europe and of 25.7% to C29 million in the US. The Rest
of the World region added C14 million.
Overall annual group sales in Brazil that rose by just over a
third – or by 6.9% excluding generics – to C1.38 billion contributed
to Sanofi’s total Emerging Markets turnover up 9.3% at constant
exchange rates to C11.3 billion. “New initiatives are underway to
further expand our footprint in these markets,” stated chairman and
interim chief executive officer Serge Weinberg, pledging to “dedicate
additional resources to leverage our leadership position”. Emerging
Markets made up a third of group turnover that rose by 2.5% as
reported, and by 4.9% in constant currencies, to C33.8 billion. G
MANUFACTURING
FDA okays Polpharma plants
P
rivately-owned Polpharma has told Generics bulletin that its active
pharmaceutical ingredient (API) manufacturing facilities in January
this year passed a US Food and Drug Administration (FDA) inspection
with no Form 483 observations. The Polish firm noted that this was
the fourth time in 11 years the FDA had reported no manufacturing
deficiencies at its API plants, following previous inspections in
2004, 2009 and 2012.
The group – which claims to be “among the top-20 generic drug
manufacturers in the world, and a significant European producer of
APIs” – has seven manufacturing plants and six research and
development centres in Poland, Russia and Kazakhstan.
Polpharma’s Chimfarm subsidiary in Kazakhstan has just opened
an injectables unit at its facility in Shymkent as part of the
company’s “major investment project” aimed at expanding its production
capacities. The unit – which should produce over 100 million ampoules
in its first year of production – has an annual capacity of filling 300
million injectable ampoules, 2 million bags and 2 million vials.
Chimfarm – which is investing around US$100 million in the
project – has also started modernising its production lines for solid-dose
forms and antibiotic powder filling.
G
BUSINESS STRATEGY/SECOND-QUARTER RESULTS
Lannett turns gaze
to Western Europe
L
annett remains interested in globalising through acquisitions,
and is focused on opportunities in Western Europe, according to
chief executive officer Arthur Bedrosian.
Speaking to investors as Lannett reported sales ahead by 70.5%
to US$115 million in its financial second quarter ended 31 December
2014, Bedrosian revealed that Lannett had conducted due-diligence
evaluations of two companies, one of which was an “attractive company”
that would be a “good candidate” for a tax-favourable inversion move.
But ultimately, Bedrosian insisted, an accretive transaction was
Lannett’s priority as the company sought to close its first transaction.
Lannett recently enlisted the global expertise and acquisitions
experience of Teva’s Americas Technical Operations head, Michael
Bogda, appointing him as company president in lieu of Bedrosian
(Generics bulletin, 16 January 2015, page 30).
Investors did not quiz Bedrosian on the federal investigation
surrounding Lannett in relation to the company’s pricing practices,
for which it was recently served with a grand jury subpoena seeking
corporate documents (Generics bulletin, 16 January 2015, page 4).
As Figure 1 shows, those price increases caused sales in several
of Lannett’s therapeutic categories to soar ahead, including a near
fifteen-fold increase in turnover from the company’s gallstone
treatments, while the US firm’s biggest sellers – its thyroid-deficiency
treatments such as levothyroxine – rose by 69.7% to US$44.5 million.
In total, price increases added US$50.9 million to Lannett’s sales,
comfortably outstripping a US$3.4 million hit from reduced volumes.
During its financial second quarter, the US firm received final
approval for a generic version of Oak Pharmaceuticals’ Cosopt
(dorzolamide/timolol) 2%/0.5% ophthalmic solution (Generics
bulletin, 16 January 2015, page 20), although Bedrosian conceded
that sales were expected to be “modest” as Lannett was a late entrant to
market. The US firm currently has 20 abbreviated new drug applications
(ANDAs) pending US approval, five of which contain paragraph IV
patent challenges, including generic Thalomid (thalidomide) that is
the subject of litigation versus Celgene.
With research and development and other operating expenses
only slightly higher than in the prior-year quarter, Lannett’s
operating profit soared by 162% to US$66.5 million.
G
Second-quarter sales Change Proportion
(US$ millions)
(%)
of total (%)
Thyroid deficiency
Cardiovascular
Gallstone
Pain management
Migraine
Glaucoma
Antibiotic
Gout
Obesity
Other
44.5
18.3
16.7
7.6
6.9
5.5
3.3
3.0
1.0
7.9
+69.7
+8.3
+1372.7
+11.4
+195.4
+272.2
-22.8
+48.8
+12.9
+52.0
39
16
15
7
6
5
3
3
1
7
Lannett
114.8
+70.5
100
Figure 1: Breakdown by therapeutic category of Lannett’s sales in its financial
second quarter ended 31 December 2014 (Source – Lannett)
27 February 2015
GENERICS bulletin 9
COMPANY NEWS
ANNUAL RESULTS
Russia and Ukraine
hit Richter’s results
D
ouble-digit sales declines in Russia and Ukraine caused Gedeon
Richter’s Pharmaceutical turnover to decline by 3.9% to C988
million (US$1.13 billion) last year. Including the Hungarian group’s
loss-making Wholesale and Retail business, which operates mainly
in Romania, group turnover fell by 3.4% to C1.15 billion.
Pharmaceutical sales in Russia tumbled by 18.6% to C274
million, although the local-currency slide was a more modest 3.7%.
While wholesaler destocking had depleted local turnover, Richter
enjoyed “good sales performances” from oral contraceptives, Diroton
(lisinopril), Mydocalm (tolperisone), and Panangin (asparaginates).
The firm blamed “more strict receivables control and voluntary
shipment restrictions” amid the local political and economic upheaval
for its turnover in Ukraine plummeting by 23.0% to C55.0 million.
That fall was offset in part by sales in other Commonwealth of
Annual sales
(CC millions)
Change
(%)
Proportion
of total (%)
Russia/CIS
European Union*
Hungary
US
China
Latin America
Rest of World
Pharmaceutical
407.3
321.2
103.5
52.1
44.1
18.8
41.4
988.4
-15.1
+2.5
+1.3
+9.5
+25.6
+66.4
+5.3
-3.9
36
28
10
4
4
2
4
86
Wholesale & Retail
179.5
-0.5
16
Eliminations/Other
-22.2
–
-2
1,145.7
-3.4
100
Gedeon Richter
* excluding Hungary
Figure 1: Breakdown of Gedeon Richter’s sales in 2014 (Source – Gedeon Richter)
Independent States (CIS) members rising by 9.0% to C78.5 million.
Total sales in the region fell by 15.1% to C407 million (see Figure 1).
Pharmaceutical turnover in the European Union (EU), excluding
Hungary, advanced by 2.5% to C321 million. This came despite a
13.5% drop to C64.1 million in Poland amid wholesaler destocking
and a mild flu season hitting sales of Groprinosin (inosine pranobex).
Sales in Romania fell by 11.1% to C28.8 million even after the
fourth-quarter introduction of Coltowan (ezetimibe), while turnover
in the Czech Republic was 8.8% lower at C24.8 million.
In Western Europe, stronger sales of Esmya (ulipristal acetate)
helped to push up Pharmaceutical turnover by 2.9% to C66.5 million
in Germany, by around two-fifths to C18.0 million in France, and
by about 70% to C13.9 million in the UK. Spanish sales doubled to
C14.8 million on the “good performance of Esmya”.
The Hungarian group said its reported 1.3% sales rise to C104
million in its domestic market equated to a local-currency advance
of 5.4% as the firm launched Ossica (ibandronate), Panagin Forte
(asparaginates) and zoledronic acid towards the end of last year.
In the US, turnover increased by 9.5% to C52.1 million “from
a low base” on higher sales of finished-dose finasteride and the Plan
B One Step (levonorgestrel) emergency contraceptive.
Lower gross margins and a lack of milestone payments cut the
group’s operating profit by 18.9% to C127 million.
G
10 GENERICS bulletin
27 February 2015
IN BRIEF
PAR PHARMACEUTICAL expects to record a turnover of US$1.31
billion for 2014. Generic Entocort EC (budesonide) should contribute
US$143 million to that total, with rivals to Wellbutrin XL (bupropion)
and Rythmol SR (propafenone) adding US$84 million and US$76
million respectively. Sales of generic versions of Kapvay (clonidine),
Lamictal XR (lamotrigine) and Toprol XL (metoprolol) are each
set to top US$40 million, according to preliminary figures. The
US generics specialist anticipates 2014 research and development
spending of US$116 million, with a gross profit of US$474 million
and earnings before interest, tax, depreciation and amortisation
(EBITDA) of US$183 million.
PHARMASYNTEZ – which claims to be the Russia’s largest
manufacturer of tuberculosis drugs – is acquiring a production
plant located in Tyumen, Russia, from local firm YugraFarm to
produce its domestic infusion solutions, as well as hormone therapies.
The Russian company intends to invest RUB1.7 billion (US$27
million) over the next two years in modernising the facility, which
its says will comply with international good manufacturing practice
(GMP) standards and employ 250 staff.
CO-OPERATIVE PHARMACY – the UK’s third-largest pharmacy
chain with 780 stores – is to be renamed as Well following its
takeover by Bestway Group in a £620 million (US$955 million)
deal last year (Generics bulletin, 8 August 2014, page 10). Bestway
plans to invest £200 million over the next five years in expanding
the business, with the goal of lifting the chain’s annual turnover
from £750 million to £1.0 billion by 2019.
DIVI’S LABORATORIES intends to invest around Rs5.0 billion
(US$81.0 million) in setting up a third manufacturing facility in
India. The Indian bulk-drugs producer has asked the regional
government of Andhra Pradesh to allot land near Kakinada. In its
financial third quarter ended 31 December 2014, Divi’s increased
its turnover by 15% to Rs7.91 billion, but its pre-tax profit edged
up by just 2% to Rs2.78 billion.
AMNEAL has appointed GE Capital to act as its agent for a US$250
million loan. “The proceeds from this financing will be used to
fund capital expansion related to manufacturing and a distribution
to existing shareholders,” GE Capital said.
INDOCO REMEDIES reported net sales ahead by 13% to Rs2.13
billion (US$34.2 million) in the three months ended 31 December
2014. The Indian firm’s domestic turnover grew by 7% to Rs1.30
billion, while its sales outside of India expanded by 23% to
Rs833 million. Lower finance costs helped Indoco to improve its
pre-tax profit by 56% to Rs282 million.
FARMAK said it remained market leader in Ukraine, despite the
group’s turnover falling by a tenth to US$122 million last year.
Citing data from market researcher SMD, the company claimed it
ranked first by value in Ukraine, ahead of Novartis and Menarini.
JB CHEMICALS & PHARMACEUTICALS increased its net sales
by a tenth to Rs2.57 billion (US$41.3 million) in its financial third
quarter ended 31 December 2014. That growth was aided by starting
sales and distribution activities in Russia and the Commonwealth
of Independent States (CIS) last year through a wholly-owned
subsidiary. Indian formulations sales increased by 11% to Rs950
million, while formulations exports grew by 9% to Rs1.29 billion.
But active pharmaceutical ingredient (API) turnover slipped
slightly to Rs258 million.
G
COMPANY NEWS
SECOND-QUARTER RESULTS
I
R
Cambrex is growing Protopic rival peps
Iowa bulk-drugs site Perrigo’s turnover
ncreased demand for its active pharmaceutical ingredient (API)
contract-manufacturing services has led Cambrex to begin expansion
work at its US production facility in Charles City, Iowa.
Noting that this was the second such expansion in less than three
years at its Charles City complex, the US company said it expected
to invest US$45-US$50 million building an additional current good
manufacturing practice (cGMP) production unit and related infrastructure
alongside existing operations.
Slated for completion early next year, the new plant, which will
be capable of handling potent APIs, will allow Cambrex to “quickly
and efficiently further expand cGMP capacity, as future growth
requires”. It will add 70 cubic metres of reactor capacity as well as
4,200 sq m of warehouse space. Expansion work has also begun at the
US firm’s sites in Karlskoga, Sweden, and Milan, Italy, revealed Steven
Klosk, Cambrex’ president and chief executive officer.
Last year, strong demand for its exclusive and controlled-substance
products pushed Cambrex’ group turnover ahead by 17.7% to US$375
million. But increased research and development spending and a
pension-settlement charge lowered the US firm’s operating margin
by 1.6 percentage points to 14.0%. Cambrex is forecasting sales
growth of 16-20% this year.
G
Podravka invests in plant
P
odravka is building a 23,000 sq m solid-dose, semi-solids and
liquids facility in Croatia to ease capacity constraints and develop
value-added generics such as effervescent tablets, sprays, patches and
medicated chewing gum. The Croatian firm said its utilisation of
its current granulation and compression capacity was at 89%, while
semi-solids and liquids lines were working on Saturdays. Construction
of the C51.4 million (US$58.5 million) project – including a government
incentive worth up to C20.0 million – is due to start in March, with
a manufacturing licence targetted by the end of March 2017.
Podravka’s Pharmaceuticals turnover fell by 1.3% to CrK840
million (US$124 million) last year, equivalent to a 1.9% increase at
constant exchange rates.
In its home market, an estimated CrK57.2 million hit from from
reimbursement cuts imposed by the Croatian Health Insurance Fund
in May 2013 and February 2014 wiped out 7.0% volume growth as
sales fell by 10.4% to CrK396 million despite launches via its Belupo
unit including Eminens SR (ropinirole) sustained-release tablets and
Viner Mint (sildenafil) chewable tablets.
Gains in Bosnia & Herzegovina contributed to double-digit growth
to CrK225 million in the firm’s South-East Europe region. But a 16.1%
constant-currency rise in Eastern Europe became a reported 1.6% drop
to CrK162 million due to the devaluation of the Russian rouble.
Growth of more than a third to CrK49.5 million in Central
Europe came from dermatology products, entering the Polish market
and high single-digit growth in the Czech Republic.
Pharmaceuticals sales accounted for just under a quarter of the
Croatian food and beverages group’s turnover that fell by 3.4% to
CrK3.50 billion. But a Pharma operating profit down by 31.6% to
CrK80.2 million was still more than half of the group total.
G
ecent launches such an authorised generic of Astellas’ Protopic
(tacrolimus) 0.03% and 0.1% ointments and “increased volumes”
pushed up Perrigo’s Prescription Pharmaceuticals sales by 12% to
US$277 million in the US firm’s financial second quarter ended 27
December 2014. The Prescription business accounted for over a quarter
of group turnover that advanced by 9% to US$1.07 billion, largely due
to US$54 million of new-product sales and a US$79 million increase
in royalties from Biogen Idec’s sales of Tysabri (natalizumab).
Double-digit Prescription sales growth helped to offset lower
Consumer Healthcare and Nutritionals sales, while turnover from
Perrigo’s Active Pharmaceutical Ingredient (API) segment stalled
at US$30.0 million (see Figure 1).
The Protopic authorised generic launch (Generics bulletin, 5
December 2014, page 27) contributed to the Prescription segment
generating US$33 million of sales from new products. Those gains
comfortably offset a US$14 million hit from discontinuing products.
Having also introduced a US rival to Mallinckrodt’s Pennsaid
(diclofenac sodium) 1.5% topical solution in December last year, Perrigo
in January introduced an alternative to AbbVie’s Androgel (testosterone)
1.0% gel and a rival to Galderma’s Clobex (clobetasol propionate) 0.05%
spray with 180-day generic market exclusivity (Generics bulletin,
6 February 2015, page 20). And the firm has just received US Food and
Drug Administration (FDA) approval for the first generic of Novartis’
Transderm Scop (scopolamine) extended-release transdermal film.
The Prescription segment improved its second-quarter gross
margin by 1.8 percentage points to 54.0%, but “higher investments
in both clinical research and development and in growing the specialty
pharmaceuticals salesforce” following a deal for Lumara’s women’s
health portfolio contributed to its operating margin dipping by just
over a point to 39.6%. Perrigo’s group operating margin improved by
more than eight percentage points to 17.2% following prior-year charges
linked to acquiring Elan and Tysabri.
In its current financial year ending in June 2015, Perrigo expects
to generate at least US$235 million from sales of newly-launched
products. Among the firm’s pipeline is an OTC store-brand version
of Sanofi’s Nasacort Allergy 24HR (triamcinolone) nasal spray that
it plans to launch through a tie-up with Teva in time for the next US
allergy season. Perrigo is also pushing into gummy vitamins through
a recently struck alliance with Ferrara Candy.
By the end of March, Perrigo expects to close a C3.6 billion
(US$4.1 billion) deal for Belgium’s Omega Pharma that it agreed in
November last year (Generics bulletin, 14 November 2014, page 3). G
Business
segment
Second-quarter sales Change
(US$ millions)
(%)
Consumer Healthcare
Prescription Pharma
Nutritionals
Specialty Sciences
API
Other
Perrigo
Operating
margin (%)
530
277
131
87
30
18
-1
+12
-7
+1.070
±0
-4
14.1
39.6
5.5
11.0
24.7
6.4
1,072
+9
17.2*
* includes US$25.4 million of unallocated expenses
Figure 1: Breakdown by business segment of Perrigo’s sales and operating margin
in its financial second quarter ended 27 December 2014 (Source – Perrigo)
27 February 2015
GENERICS bulletin 11
COMPANY NEWS
NINE-MONTH RESULTS
L
C
Lupin grows despite Towa cuts its costs
regulatory hold-ups to improve margins
upin overcame delays in obtaining regulatory approvals to post
group turnover ahead by 5% to Rs31.4 billion (US$506 million)
in its financial third quarter ended 31 December 2014. Double-digit
advances in Europe and India pushed up Formulations sales by 7%
to Rs28.7 billion, more than countering a 7% slide to Rs2.76 billion
in active pharmaceutical ingredient (API) turnover on steep declines
in the US and Europe.
Lower raw-material costs and a 4% reduction in research and
development spending helped to boost the debt-free Indian group’s
pre-tax profit by 16% to Rs8.53 billion.
“The company’s continued focus on improving operational
efficiencies has led to sustained margins and profit growth,
notwithstanding regulatory delays that have resulted in pressures
on the top line,” remarked managing director Nilesh Gupta.
Three abbreviated new drug application (ANDA) submissions
and three approvals during the quarter left approved just over half
– 108 – of the 203 ANDAs the firm has filed with the US Food and
Third-quarter sales Change
(Rs millions)
(%)
Proportion
of total (%)
US
India
Japan
South Africa
Europe
Rest of World
Formulations
14,043
7,438
3,422
1,070
805
1,913
28,691
+4
+14
-8
+9
+15
+35
+7
45
24
11
3
2
6
91
APIs
2,758
-7
9
Lupin
31,449
+5
100
Figure 1: Breakdown by region and business of Lupin’s sales in its financial third
quarter ended 31 December 2014 (Source – Lupin)
Drug Administration (FDA). The Indian company believes it has to
date made 30 first-to-file opportunities – targeting US$13.7 billion
in annual brand sales – of which half are exclusive opportunities.
Pointing out that it had received “no [Form] 483 observations
in the past five FDA audits”, Lupin said it was market leader for 30
of the 74 US generics it marketed as of 31 December 2014. Eight US
product launches since April 2014 helped to lift US Formulations
sales by 4% to Rs14.0 billion, equivalent to a 1% local-currency rise.
European turnover climbed by 15% to Rs805 million as Lupin
“saw robust growth across all businesses”. The Indian group achieved
a 14% sales rise to Rs7.44 billion in its domestic market through
growth in chronic conditions.
In Japan – where Lupin claims to be the eighth-largest generics
player – turnover fell by 8% to Rs3.42 billion as reported, but increased
by 4% in local-currency terms. The Kyowa solid-dose business
registered a 9% turnover rise on “good matured-products growth”, but
the Irom subsidiary’s sales slipped by 1% as the injectables specialist
undertook “cost-rationalisation initiatives to enhance profitability”.
Adverse currency shifts halved the 19% local-currency growth
produced by Lupin’s Pharma Dynamics affiliate in South Africa to a
reported 9% turnover gain to Rs1.07 billion. Formulations sales up by
more than a third to Rs1.91 billion in the Rest of the World region
included the first full quarter after Lupin bought Mexican ophthalmics
firm Laboratorios Grin (Generics bulletin, 4 April 2014, page 3). G
27 February 2015
utting manufacturing costs helped Japan’s Towa to improve its
profit margins in the first nine months of its financial year ending
31 March 2015, despite price cuts mandated by the country’s National
Health Insurance (NHI) system.
As Towa’s sales for the period rose by 17.3% to ¥53.1 billion
(US$443 million), the firm’s costs of goods rose by 15.5% to ¥25.8
billion, while selling, general and administrative expenses increased
by just 12.9% to ¥18.7 billion. This gave Towa an operating profit
34.8% higher at ¥8.61 billion, and an operating margin that jumped
by 2.1 percentage points to 16.2%.
Improved profitability came despite a 17.8% increase in research
and development costs to ¥4.66 billion – of a forecasted total of
¥6.5 billion for the full financial year – as a result of Towa investing
in its development pipeline. Products launched in 2014, including
orodispersible valsartan, contributed ¥1.4 billion to sales, while
those introduced in 2013 – such as orodispersible pitavastatin –
accounted for ¥3.7 billion, or around 7% of sales.
In light of the latest figures, Towa has revised its full-year forecast
to reflect its improved profitability. The firm expects to generate an
operating profit of ¥10.0 billion – compared to its previous estimate
of ¥7.80 billion – on projected full-year sales that remain unchanged
at ¥72.0 billion. This will give Towa an operating margin of 13.9%,
rather than the 10.8% originally forecast.
G
ANNUAL RESULTS
Off-patent drugs assist Orion
O
rion says its generics are now “accounting for a greater proportion
of total sales” as several of its brands come under generic
competition. The Finnish group reported a 0.8% increase in group
turnover to C1.02 billion (US$1.15 billion) last year.
“Competition in Finland, the most important generics market for
Orion, remains intense in 2015. However, product launches continue
to support Orion’s position as market leader,” the firm stated.
Last year, sales by Orion’s Specialty Products off-patent, generics,
OTC and biosimilars division increased by 11% to C427 million. That
rise was driven in part by sales of generic entacapone more than doubling
to C26 million, as the rest of the division’s portfolio showed 7% growth.
In Finland, the division posted a 9% sales increase to C256 million,
while in Scandinavia turnover advanced by 21% to C50 million. But
the depreciation of the Russian rouble caused sales in Eastern Europe
and Russia to stall at C56 million.
Infliximab sales reached C6 million
Orion said the division had derived sales of C6 million from
marketing the Remsima (infliximab) biosimilar in Finland, Scandinavia
and the Baltic States through an agreement with South Korea’s
Celltrion. In Norway, Orion is offering discounts of up to 72%
compared to the reference brand, Remicade (see page 29).
Weaker sales of a key product reduced by a tenth to C57 million
turnover by Orion’s Fermion active pharmaceutical ingredients (APIs)
division. Proprietary Products sales fell by 4.4% to C373 million, due
in part to generic competition to Stalevo (carbidopa/levodopa/
entacapone) in Germany, while Animal Health, Diagnostics and
other operations contributed C158 million.
G
COMPANY NEWS
FIRST-QUARTER RESULTS
MANUFACTURING
Q
T
Oxycodone bulks up Siegfried sorts out
Mallinckrodt’s sales FDA Hameln letter
uadrupling sales of its bulk and finished-dose oxycodone helped
Mallinckrodt to increase its Specialty Generics turnover by 13.7%
to US$284 million in the US firm’s financial first quarter ended 26
December 2014. Of that total, US$234 million was generated in the
US, US$23.7 million in Europe, the Middle East and Africa (EMEA),
and US$26.7 million in other markets.
The oxycodone gains following “strategic pricing initiatives”
more than made up for the blow of Mallinckrodt’s rivals to Janssen’s
Concerta (methylphenidate) extended-release tablets – along with
Kudco’s generic versions – losing their AB-rating for therapeutic
equivalence to the brand last year (Generics bulletin, 5 December
2014, page 23). The firm’s methylphenidate sales fell by 13.7% to
US$48.6 million (see Figure 1).
Mark Trudeau, Mallinckrodt’s president and chief executive
officer, said the firm planned to keep methylphenidate on the market
as a BX-rated product – indicating insufficient data to determine
therapeutic equivalence – for the “foreseeable future”. “Clearly, as a
BX-rated product, it’s going to be at a lower revenue rate [in 2015]
than it was in 2014,” Trudeau commented, reiterating that Mallinckrodt
believed “very strongly” that the product was safe and effective.
The company had acted quickly to launch a line of hydrocodone
Schedule II combination products following reclassification of the
controlled substance, he pointed out.
Meanwhile, Trudeau said that Mallinckrodt was “aggressively
pursuing” a number of acquisitions, based on the firm’s strong cash
flow and operational capability.
The bulk of Mallinckrodt’s 60.4% group turnover rise to US$866
million came from Specialty Brands sales rising by more than six
times to US$374 million as the US firm added US$338 million through
incorporating the Ofirmev (acetaminophen) and Acthar (corticotropin)
injectables that it purchased in March and August last year respectively.
This dwarfed a turnover slide of almost a tenth to US$199
million in Mallinckrodt’s Medical Imaging segment, which the US
firm attributed to restructuring initiatives and adverse exchange rates.
Even with a US$126 million intangible amortisation charge linked
largely to the Acthar deal, Mallinckrodt’s operating profit jumped by
74.3% to US$127 million. Oxycodone pushed up the Specialty Generics
segment’s operating margin by almost a percentage point to 49.4%. G
First-quarter sales
(US$ millions)
Change
(%)
Operating
margin (%)
373.6
+526.8
39.7
Methylphenidate ER
48.6
Oxycodone
47.0
Hydrocodone
34.0
Other controlled substances 111.9
Other generics
42.7
Specialty Generics
284.2
-13.7
+305.2
+13.0
-6.9
+34.7
+13.7
–
–
–
–
–
49.4
199.3
-8.8
8.7
9.2
-24.0
–
866.3
+60.4
14.7*
Specialty Brands
Medical Imaging
Other
Mallinckrodt
* includes US$179 million of unallocated corporate expenses
Figure 1: Breakdown of Mallinckrodt’s sales in its financial first quarter ended
26 December 2014 (Source – Mallinckrodt)
he US Food and Drug Administration (FDA) has rescinded a
warning letter that the agency issued in 2012 against a Hameln
Pharma sterile injectables facility in Germany that has just been
acquired by Swiss group Siegfried.
In a brief close-out letter, the agency said corrective actions
undertaken at the factory in Hamelin, Germany, appeared to have
addressed the violations listed in the warning letter from December
2012. That letter – which resulted from an inspection conducted in June
2012 – highlighted issues with staff training and systems for monitoring
environmental conditions (Generics bulletin, 1 February 2013, page 6).
“Following revocation of the warning letter, the path has been
cleared for the Hameln Pharma facility to be immediately and fully
integrated into Siegfried’s worldwide compliance system,” stated
the Swiss group, which bought the German injectables contract
manufacturer towards the end of last year (Generics bulletin, 5
December 2014, page 1).
German authorities cleared facility
Pointing out that one of its US customers could now resume imports
of products made at the Hameln site, Siegfried said German regulatory
authorities had recently renewed Hameln’s good manufacturing
practice (GMP) certificate.
At the time the SFr60 million (US$63 million) deal for Hameln
was announced, a spokesperson for Siegfried told Generics bulletin
the Swiss firm was confident that the FDA would soon lift the warning
letter following a recent re-inspection.
G
INVESTIGATIONS
Impax investigated for delays
P
atent settlement agreements reached by Impax for three US brands –
Shire’s Adderall XR (amphetamine salts), Endo’s Opana ER
(oxymorphone) and Pfizer’s Effexor XR (venlafaxine) – are being
investigated by Alaska’s attorney-general to determine whether they
violated state law by unlawfully delaying generic entry in Alaska.
The US firm said it intended to cooperate with the investigation,
and would produce documents and information in response to the
civil investigative demands it had received for each product. “To the
knowledge of the company,” commented Impax, “no proceedings
have been initiated at this time.”
G
Alembic advances in India
A
12% increase in Indian Formulations sales was largely responsible
for Alembic Pharmaceuticals increasing its turnover by 6% to
Rs5.15 billion (US$82.8 million) in its financial third quarter ended
31 December 2014.
With sales of Rs2.83 billion, Indian Formulations accounted for
55% of the group total as International Formulations turnover fell by
4% to Rs1.47 billion. Active pharmaceutical ingredient (API) sales rose
by 7% to Rs813 million, while export incentives added Rs36.5 million.
The group’s pre-tax profit edged up by 1% to Rs900 million.
G
27 February 2015
COMPANY NEWS
Glenmark grows its
sales as profits slide
D
ouble-digit sales growth in India and Europe, coupled with
turnover in Latin America more than doubling, helped Glenmark
overcome a sales tumble of almost a third in its Rest of the World
business as the Indian company’s group turnover increased by 6.2%
to Rs17.0 billion (US$273 million) in its financial third quarter
ended 31 December 2014.
But a ramp up in material costs and purchase of stock-in-trade
caused Glenmark’s pre-tax profit to tumble by 31.4% to Rs1.51 billion.
In the firm’s Rest of the World segment, sales fell by 31.3% to
Rs2.07 billion, due in part to currency depreciation throughout the
business. However, Glenn Saldanha, the Indian firm’s chairman and
managing director, revealed that the company had been boosted in
Russia by a recent approval for generic Seretide (fluticasone/salmeterol),
and was also anticipating a further “two or three large approvals”.
“We have a positive view of Russia, it is very profitable and our
respiratory portfolio is doing very well,” Saldanha told investors, adding
that the company would not look to capitalise in the country with price
increases and would instead adopt a “wait and watch approach”.
As Figure 1 shows, Glenmark’s sales in the US slid by 2.7% to
Rs5.07 billion. Saldanha blamed a slowdown in US generic approvals
– evidenced by Glenmark receiving just one US Food and Drug
Administration (FDA) approval during the quarter, for rivals to
AstraZeneca’s Prilosec (omeprazole) 10mg, 20mg and 40mg delayedrelease capsules – and channel consolidation for that turnover fall.
But, Saldanha insisted, the company’s fortunes in the US would
turn as product approvals accelerated, beginning in Glenmark’s current
Region
Third-quarter sales
(Rs millions)
Change
(%)
Proportion
of total (%)
US
India
Latin America
Rest of world
Europe
APIs
5,072
4,331
2,344
2,071
1,730
1,465
-2.7
+13.6
+105.8
-31.3
+27.3
-1.0
30
25
14
12
10
9
Glenmark
17,013
+6.2
100
Figure 1: Breakdown by business segment and region of Glenmark Pharmaceuticals’
sales in its financial third quarter ended 31 December 2014 (Source – Glenmark)
financial quarter. The firm also had “a couple of sure launches”,
including generic desmopressin, according to Glenmark’s US head,
Robert Matsuk.
The Indian firm’s domestic sales rose by 13.6% to Rs4.33 billion,
as Glenmark improved its market share for cardiovascular and
respiratory disease treatments, anti-infectives and diabetes drugs.
However, these gains were partially offset by losing share for
gynaecology and dermatology drugs.
Elsewhere, Latin American sales continued to soar, more than
doubling to Rs2.34 billion, thanks to surges in Mexico and Venezuela.
“We’ve launched a respiratory product in Brazil, but still continue to
struggle for product approvals in the country,” Glenmark revealed.
Meanwhile, despite sales growing by more than a quarter to
Rs1.73 billion in Europe, Glenmark said it had struggled in Romania
due to the “challenging business environment”. However, this was
comfortably offset by strong growth in the UK, Germany and Poland. G
27 February 2015
IN BRIEF
DSM said “solid growth and operational improvements at its Yushu,
China, intermediates plant” helped to push up turnover by its DSM
Sinochem affiliate by 8% to C399 million (US$452 million) last year.
LUPIN said its manufacturing facility at Pithampur near Indore,
India, had received six ‘Form 483’ observations following an
audit by the US Food and Drug Administration (FDA) in January
this year. “Since then, the Indore facility has received one
abbreviated new drug application (ANDA) approval and two sitetransfer approvals,” the Indian group noted, adding that its LBC
bioresearch centre in Pune, India, had passed an FDA inspection
without any observations. Lupin has just secured US approval for
bimatoprost 0.03% ophthalmic solution from the Indore facility.
NATCO PHARMA reported consolidated turnover down by 4%
to Rs1.95 billion (US$31.4 million) in its financial third quarter
ended 31 December 2014. An exceptional charge of Rs151 million
for settling a legal case contributed to the Indian firm’s pre-tax
profit halving to Rs191 million.
JEAN COUTU said sales by its Pro Doc generics operation advanced
by 6% to C$50.7 million (US$42.0 million) in its financial third
quarter ended 29 November 2014. The Pro Doc rise helped to push
up the Canadian retailing group’s turnover by 3% to C$737 million.
DISHMAN said a three-day inspection by the US Food and Drug
Administration (FDA) – initially planned to last five days – confirmed
that its site in Veenendaal, the Netherlands, complied with current
good manufacturing practice (cGMP) standards. The plant
specialises in making vitamin D analogues. Three-quarters of the
Indian group’s turnover that moved ahead ahead by 23% to Rs3.86
billion (US$62.0 million) in the three months ended 31 December
2014 came from contract research and manufacturing services,
with the other quarter derived from other activities such as sales
of bulk drugs and intermediates.
STRIDES ARCOLAB reported sales that stalled at Rs3.26
billion (US$52.5 million) in its financial third quarter ended 31
December 2014, during which it filed four products with the US
Food and Drug Administration (FDA) and received approval for
calcitriol soft-gel capsules. The Indian firm’s Institutional business
accounted for Rs1.28 billion of that total, emerging markets
Rs1.01 billion and regulated markets Rs966 million.
VERTEX has completed construction of a manufacturing facility
in Saint Petersburg, Russia, following a RUB1.8 billion (US$27.1
million) investment. Intended to comply with international good
manufacturing practice (GMP) standards, the plant will have an
annual capacity of around 70 million packs, covering tablets, capsules,
ointments, creams, and sprays. The firm expects to start production,
including for contract-manufacturing customers, in the third quarter
of this year.
AJANTA PHARMA is qualifying an oral solid-dose facility in
Dahej, India, and expects to produce regulatory-filing batches within
the next few months. In its financial third quarter ended 31 December
2014, the Indian formulations specialist increased its turnover by
21% to Rs3.63 billion (US$58.4 million). Ajanta’s domestic sales
rose by 35% to Rs1.32 billion, while its turnover in emerging markets
grew by 15% to Rs2.23 million, comprising Rs1.10 billion from
Africa, Rs1.09 billion from Asia and Rs40 million from Latin
America. In the US, the firm has 23 abbreviated new drug applications
(ANDAs) pending approval.
G
MARKET NEWS
INTELLECTUAL PROPERTY
REGULATORY AFFAIRS
G
F
Australia can allow FDA reopens debate
compulsory licensing on label change rule
enerics manufacturers can now apply to Australia’s Federal Court
to obtain compulsory licences that will allow them to produce
patented drugs for export to developing countries facing health crises.
The country’s Intellectual Property Laws Amendment Act 2015 passed
by the country’s Senate on 9 February permits the court to determine
appropriate remuneration for the patent holder.
A specific section of the amendments dealing with compulsory
licences for patented pharmaceuticals sets out the conditions that must
be met. The court may order a compulsory licence “if the proposed
use of the pharmaceutical product is to address a public health issue
in the eligible importing country”, either in a national emergency or
“by the public non-commercial use of the product”.
Noting that such an order may be amended or revoked by the court,
the amendments also state that the patentee “must be paid an agreed
amount of remuneration, or an amount of remuneration determined
by the court”.
This “adequate remuneration” decided by the court would take
into account “the economic value to the eligible importing country of
the use of the patented pharmaceutical invention”.
If the compulsory licensing order is granted on the basis of a
“public non-commercial use of the product”, the applicant must first
give the patentee a notice seeking an authorisation to exploit the
patented invention for non-commercial use. Furthermore, the applicant
must have within 30 days of this notice tried without success to obtain
such an authorisation “on reasonable terms and conditions”.
Applicants and importing countries must also take “reasonable
measures” to prevent pharmaceuticals that are exported from Australia
under such a licence from being used “for a purpose other than the
purpose of addressing the public health problem”.
Separately, the amendments include a broader section on
compulsory licensing in general that allows the Federal Court to grant
a licence in Australia “if the reasonable requirements of the public
are not being met with respect to a patented invention”.
Despite pharmaceuticals being governed by the separate specific
compulsory licensing measures, the general section notes, this “does
not prevent a compulsory licence from being ordered under this part
in relation to such an invention”.
G
REGULATORY AFFAIRS
Quebec lifts substitution bar
C
anadian province Quebec expects to save around C$40 million
(US$32 million) annually by removing doctors’ ability to mark
prescriptions as non-substitutable, according to provincial health
minister Gaétan Barrette. From 24 April, pharmacists will be able
to substitute a generic even when the prescription is marked “do
not substitute”, Barrette announced, although for valid prescriptions
issued before this date the direction not to substitute would be
honoured by pharmacists until 1 June.
Exceptions to the rule included ‘class seven’ medicines – a group
of drugs for which treatment needed to be monitored very closely or
which required very precise dosing – such as immunosuppressants,
Barrette explained. Substitution will also still be able to be blocked in
cases such as patient allergies to inactive ingredients – such as sugars
or colourants – that were present in generics but not in the brand. G
urther comments on a proposed rule to change requirements for
generic labelling are being solicited by the US Food and Drug
Administration (FDA) both in writing and at a public meeting.
On 27 March, the agency plans to hold a meeting at its White
Oak campus in Maryland to “listen to comments on the proposed
rule” – which would require generics firms to update safety information
using the same ‘changes being effected’ (CBE) process as originators
– as well as alternatives to the proposal that was first made in late
2013 (Generics bulletin, 15 November 2013, page 1). Attendees must
register by 20 March, while comments can be made until 27 April.
“Stakeholders may present or comment on the proposed rule
or any alternative proposals intended to improve communication of
important newly-acquired drug safety information to healthcare
professionals and the public,” the FDA said. The meeting comes in
response to requests from the US Generic Pharmaceutical Association
(GPhA) and brand industry association PhRMA.
The GPhA has repeatedly voiced its opposition to the proposed
rule, citing concerns that it could lead to multiple labels, causing
confusion. The association last year threatened legal action if the FDA
released an unchanged final rule as originally scheduled in December
(Generics bulletin, 3 October 2014, page 9). The FDA subsequently
deferred its decision, having received “a great deal of public input
from various stakeholders during the comment period” (Generics
bulletin, 5 December 2014, page 15).
G
REGULATORY AFFAIRS
EU clarifies SPC import law
F
irms that imported medicines into a European Union (EU) member
state in which the product enjoyed supplementary protection
certificate (SPC) protection from a country that only became an EU
member state in 2004 – and in which similar SPC protection was not
available – can rely on the EU’s ‘specific mechanism’ to justify the
import, provided that the SPC holder did not oppose it during the
mechanism’s one-month waiting period, the Court of Justice of the
EU (CJEU) has ruled (Generics bulletin, 3 November 2014, page 14).
The case involved Sigma and Pharma XL importing Merck, Sharp
and Dohme’s Singulair (montelukast) from Poland and repackaging
it for the UK market in 2010. While an SPC in the UK – which
expired on 24 February 2014 – existed based on European patent
EP0,480,717, similar protection was not available in Poland.
Under the ‘specific mechanism’, patent or SPC holders can give
notification of their intent to oppose parties from importing a product
from the Czech Republic, Estonia, Latvia, Lithuania, Hungary, Poland,
Slovenia or Slovakia into a state where the product is protected. G
IN BRIEF
BIO – the US Biotechnology Industry Organization – has claimed that
a proposed patent-reform bill would “undermine the ability of
legitimate patent owners to commercialise their inventions and enforce
their patent rights against infringers”. US Representative Bob Goodlatte
insisted that the Innovation Act would help “curb abusive patent
litigation” based on “weak or poorly-granted patents”.
G
27 February 2015
MARKET NEWS
MARKET RESEARCH
France must address
declining sales trend
A
“rapid reaction” is needed to address declining turnover and
“stagnant” volumes in France’s generics market, according to
local industry association Gemme. Generics sales fell by 4% to
C3.30 billion (US$3.74 million) in 2014, Gemme said, citing data
from local market researcher GERS, while volumes improved by
just 2% to 800 million units.
GERS’ figures indicated that generics enjoyed an 18% value
share of France’s reimbursable pharmaceutical market, and a share
of almost a third by volume.
Moreover, Gemme pointed out, if a constant ‘perimeter’ of
products was applied – excluding from the comparison new launches
in 2014 – value sales would have fallen by 8% to C3.16 billion last
year, while volumes would have declined by 2% to 769 million
units. “Market progress is only being supported by new launches,”
the association observed.
Insisting that the “worrying” decline demonstrated the “absolute
necessity” to overhaul France’s prescribing structure, Gemme also
noted that the fall in value was due to “massive price cuts applied
in 2014”, which had wiped around C220 million off generics turnover.
This “blind” policy of price cuts was putting at risk continuity of
supply, the association warned.
Gemme’s president, Pascal Brière, noted that using generic
medicines had saved France around C2 billion in 2014. But “if generic
medicines were used in the same proportions as in Germany and the
UK”, he noted, “these savings could be doubled”.
Meanwhile, a report by market researcher GlobalData has
forecasted that France’s overall pharmaceutical market will achieve
a compound annual growth rate (CAGR) of just 0.7% from 2014 to
2020, “restricted by an increasing focus on generic drugs”.
While France had been a “relatively late entrant to the generics
market”, GlobalData said, the researcher expected generics volumes
to “shift closer to levels seen in the rest of Europe”, restricting overall
growth for pharmaceuticals.
G
REGULATORY AFFAIRS
US looks for biologics savings
R
educing data exclusivity for branded biologics from 12 years to
seven and prohibiting additional exclusivity periods for such drugs
for “minor changes in product formulations” would save the US around
US$16 billion over 10 years, according to proposals set out in the
country’s 2016 budget. Other measures aimed at lowering costs for
the Medicaid insurance programme – including collecting additional
rebates for generics with prices that grow faster than inflation, and
excluding authorised generics from average manufacturer price
calculations – would save a further US$6.3 billion, the document states.
Local brand biologics association the Biotechnology Industry
Organization (BIO) said reducing data exclusivity would “jeopardise
the careful, overwhelmingly bipartisan balance established in the law
to reduce costs, expand access, and encourage continued innovation”.
Meanwhile, the US Food and Drug Administration (FDA) said
it had requested an overall budget of US$4.9 billion, which FDA
Commissioner Margaret Hamburg said “accurately reflects the
challenges FDA faces in a global regulatory environment, which is
becoming increasingly complex and scientifically demanding”. G
27 February 2015
IN BRIEF
CGPA – the Canadian Generic Pharmaceutical Association – has
welcomed savings that will be generated through a healthcare
‘action plan’ set out by the government of Ontario, Canada. However,
the association insisted that higher usage of generics was essential
to unlock greater savings in the Canadian province. “If Ontario’s
utilisation of generic drugs increased to the same levels as in the
US,” the association said, stating that generics were dispensed
to fill 86% of US prescriptions, “it would save the province’s
healthcare system more than C$2.6 billion (US$2.1 billion) in
the first year alone.”
ROMANIA’s mandatory pharmaceutical clawback rising to more
than 25% in the last quarter of 2014 is “unsustainable” and will
be “catastrophic for both patients and generic manufacturers”,
according to local generics industry association APMGR. Noting
that the 25.23% clawback was “the highest level calculated to date”,
APMGR’s president, Dragos Damian, said the rise – from 20.92%
in the third quarter of 2014 – did “not correlate in any way to internal
company data on growth in drug consumption”. The clawback had
already forced generics firms to cut 300 jobs and reduce production
by a tenth in 2014, APMGR noted, appealing to Romania’s
government to intervene in the clawback calculation.
SPAIN must introduce a national policy framework to encourage
the uptake of biosimilars, local generics industry association Aeseg
has told a conference including representatives from the country’s
congress and senate. Aeseg’s director-general Ángel Luis Rodríguez
de la Cuerda said specific rules recognising the special characteristics
of biosimilars were needed, rather than relying on the existing
reference-pricing system for small-molecule generics.
SOUTH AFRICA will allow a maximum increase of 7.50% in the
country’s Single Exit Price (SEP), the uniform price for each
product that manufacturers must offer to all private customers.
Companies have until 13 March to submit revised prices. The
increase – which follows a 5.82% rise last year (Generics bulletin,
14 February 2014, page 9) – does not apply to products introduced
after 23 December 2014.
AUSTRALIA must address “significant market barriers” to the
regulation and reimbursement of biosimilars, according to the
country’s Generic Medicines Industry Association (GMiA). Market
entry barriers – also including obstacles to prescribing and dispensing
biosimilars – need “urgent attention”, the GMiA said, recommending
“the implementation of a clear and predictable market access
pathway, with uptake drivers, for biosimilars”.
RUSSIA’s Civic Chamber has urged the country’s Ministry of
Health to launch an information campaign to advise the public of
domestically-produced generic alternatives to branded medicines.
The Civic Chamber claimed that large pharmaceutical firms based
outside Russia were providing financial incentives for doctors and
pharmacists to prescribe and dispense originator products at the
same time as “unreasonable” price increases were being applied
to certain brands.
QATAR’s Supreme Council of Health (SCH) has cut the prices of
457 generics by an average of 28.5% as part of a scheme to unify
import prices for Gulf Cooperation Council countries. Noting that
the drugs included cardiovascular, endocrine, musculoskeletal,
dermatological and gastrointestinal treatments, the SCH said some
medicines had prices cut by as much as four-fifths. A further wave
of price cuts will be implemented in the second half of this year. G
MARKET NEWS
REGULATORY AFFAIRS
MARKET RESEARCH
R
educing unnecessary litigation and accelerating approvals of
abbreviated new drug applications (ANDAs) and hybrid 505(b)(2)
applications are among the stated goals of a proposed rule the US Food
and Drug Administration (FDA) has released for public comment
until 7 May. Having for the past decade implemented the 2003
Medicare Modernization Act (MMA) directly from the statute, the
FDA now plans to amend its regulations to codify parts of the act
covering 30-month stays on approval and other matters not related to
180-day generic market exclusivity.
Among the proposed measures are: tackling originators including
overly broad use codes for patents listed in the FDA’s Orange Book;
treating original and reissued patents as a ‘single bundle’ of patent
rights; and clarifying the agency’s practices on patent information that
is submitted late. The FDA is also proposing to accept paragraph IV
certifications to newly-listed patents only from the first working day
after the patent is published in the Orange Book.
Also included in the proposals are plans to revise the content that
must be included in notices of paragraph IV certifications. The FDA
also plans to “clarify and augment the patent certification requirements
for amendments and supplements to 505(b)(2) applications and ANDAs
to ensure that changes to the drug product that could be protected by
patent are accompanied by a new patent certification”.
Another rule involves requiring 505(b)(2) applicants to identify
a pharmaceutically equivalent product if one is already approved. This
is “to help ensure that the 505(b)(2) pathway is not used to circumvent
the statutory patent certification obligations that would have applied
if the product was not ineligible for approval in an ANDA”.
The FDA also intends to “codify current practice” by clarifying
that 30-month stays of approval for ANDAs or 505(b)(2) applications
begin on “the later of the date of receipt of notice of paragraph IV
certification by any owner of the listed patent or by the new drug
application (NDA) holder who is an exclusive licensee”.
The FDA said the rule’s annual costs of US$91,400 would be
outweighed by benefits of around US$194,300. The agency has also
“identified, but is unable to quantify, impacts from proposed changes to
submitted patent information and the implementation of an administrative
consequence for ANDA applicants who fail to provide notice of a
paragraph IV certification within the timeframe required”.
G
C
REGULATORY AFFAIRS
REGULATORY AFFAIRS
P
E
FDA unveils plans to Canada will require
codify rules on stays shortage notification
anada will require manufacturers to publicly report drug
shortages “for Canadians to better plan for their health and
safety”, according to draft regulations set out by the country’s
government. “By providing advanced warning of upcoming shortages,
Canadians will be able to better proactively work with their healthcare
professionals to find alternative options,” said Health Canada.
Companies failing to comply will face fines and penalties.
The “mandatory reporting system” would see “timely,
comprehensive and reliable information on actual and anticipated
drug shortages” made available on an independent third-party website,
Health Canada said. “While this new website and the regulations
are being developed, manufacturers are expected to voluntarily
post information on all shortages on the industry-run website.”
“To reflect and encourage industry accountability, a public
notification register has been launched on Health Canada’s website
that lists all the manufacturers that fail to voluntarily post their
shortages,” the agency said. Federal health minister Rona Ambrose
said this would help to “name and shame” manufacturers who fail
to provide voluntary notice.
Jim Keon, president of the Canadian Generic Pharmaceutical
Association (CGPA), said the association’s members were currently
reporting shortages on the voluntary website “and will comply with any
new requirements”. The CGPA and its members had “taken an active
leadership role” to lessen the impact of drug shortages, Keon insisted.
As well as working with the Canadian government and other
stakeholders through the multi-stakeholder steering committee on
drug shortages (MSSC), the CGPA noted that it had also developed
a specific protocol for generics firms to notify and communicate drug
shortages. “CGPA will continue to work with other stakeholders to
address the root causes of drug shortages,” the association stated.
Voicing support for the government proposals, Canadian brand
industry association Rx&D said it was “committed to working with
officials to ensure the smooth implementation of a mandatory reporting
system”. Noting that its members were already committed to voluntarily
reporting shortages publicly – even if “the same cannot be said for
some companies outside of our association” – Rx&D claimed that
“in general, four out of five drug shortages are associated with
generic pharmaceutical companies”.
G
Ukraine urges a single agency West Africa seeks alignment
roposals to set up a single medicines agency for drug control and
registration in Ukraine have been released for public consultation
by the country’s Ministry of Health as part of efforts to “harmonise
the country’s medicines regulations to European standards”.
At present, procedures for drug licensing, registration, import,
safety and quality control, as well as inspection are controlled by
separate state authorities including the Ministry of Health and the
country’s Service for Medicines. This, the Ministry of Health says,
results in unnecessary duplication.
Citing countries that have already such agencies in place, including
the Czech Republic, France, the UK and the US, the Ministry of Health
believes that implementing a “one-stop-shop” for all types of licences
and permits will benefit the industry.
G
nsuring “rapid access to safe and effective medicines of good
quality for the treatment of priority diseases” is the goal of a
medicines registration harmonisation project that has been launched
in West Africa. Led by the New Partnership for Africa’s Development
(NEPAD) – an “African Union strategic framework” – through its
technical working group on medicines policy and regulatory reforms,
the initiative also includes other African regulatory bodies as well
as the World Health Organization (WHO) and United Nations (UN).
“Most countries that have policies in place have not developed
their implementation plans,” the NEPAD pointed out. “This creates
a gap in the execution of the existing policies and in turn affects local
medicines regulation.” A common action plan for the entire West
Africa region is envisaged.
G
27 February 2015
Full Pg Adv.1 23-2-15_Layout 1 23/02/2015 14:19 Page 1
Sponsoring an Award will get you
noticed by the global generics and
biosimilars industries.
Contact awards@generics-bulletin.com
for more details.
Awards Presentation & Cocktail Reception. Madrid, Spain,Tuesday 13 October 2015
Visit www.generics-bulletin.com Email awards@generics-bulletin.com Call +44 1564 777550
Awards sponsored by:
MARKET NEWS
REGULATORY AFFAIRS
REGULATORY AFFAIRS
M
I
Russia could require Input is invited over
new round of tests US interchangeability
anufacturers of generics that are registered in Russia before 1
July 2015 may have to rerun trials demonstrating that their
versions can be considered as interchangeable with equivalent brands,
according to draft legislation on approval procedures for determining
interchangeability between medicines that have been developed by
the country’s Ministry of Health. However, herbal and homeopathic
products, as well as medicines that have been marketed for more than
20 years, are exempt from the requirement.
The draft – which has been released for public consultation until
13 April – is split into five sections covering general provisions;
interchangeability criteria; procedures for determining interchangeability
of first-time registered medicines; medicines registered before 1 July;
and procedures for verifying interchangeability. If passed, it will
complement other bioequivalence legislation that is expected to come
into force on 1 July (Generics bulletin, 5 December 2014, page 15).
Meanwhile, Nikolai Gerasimenko, deputy chairman of the Russian
parliament’s health committee, has urged the country to review import
duties on pharmaceutical substances and certain medicines to help
bolster the domestic pharmaceutical industry as part of Russia’s “Pharma
2020 strategy”. During a parliamentary debate, Gerasimenko proposed
temporarily to introduce a reduced or zero rate of customs duties on
imported substances and vital drugs until more favourable conditions
for local manufacturing were met.
“According to the Pharma 2020 strategy, 90% of pharmaceuticals
should be produced locally by 2018”, Gerasimenko noted. “However,
90% of Russian drugs are made using imported components”.
Moreover, plans for setting up production facilities for active substances
in Russia had not been laid out yet, he emphasised.
At the same time, Russia’s deputy prime minister, Igor Shuvalov,
has proposed setting up a pilot project by 2018 to help reduce medicines
costs by introducing a regulatory framework for parallel imports of
medicines into the country.
However, local manufacturers opposed to the scheme have warned
that the Russian pharmacopeia is “very different” to that of Europe,
insisting that further regulatory harmonisation is needed. Moreover,
they have raised concerns over labels, packaging and instructions
appearing in a foreign language.
G
REGULATORY AFFAIRS
Swiss not affected by GVK
N
one of the medicines that have been called into question in the
European Union (EU) over bioequivalence studies conducted by
GVK Biosciences are currently on the Swiss market, according to
local medicines agency Swissmedic.
After the European Medicines Agency (EMA) recommended the
European Commission to suspend hundreds of marketing authorisations
in the EU based on concerns raised following an inspection of GVK
(Generics bulletin, 6 February 2015, page 17), Swissmedic said it had
confirmed through “comprehensive analysis” that no corresponding
preparations were available in Switzerland.
However, Swissmedic observed, “three preparations with export
authorisations were identified”. These authorisations – granted for
products intended exclusively for export – would now be “reviewed
in detail”, the regulator stated.
G
nterested parties have until 6 April to comment on whether the
information the US Food and Drug Administration (FDA) intends
to collect in biosimilar applications and supplements to support
interchangeability are necessary and “will have practical utility”.
The agency also wants to hear about ways to “enhance the quality,
utility and clarity” of some information while minimising the burden
on respondents. Based on its experience to date, the FDA expects
to receive five biosimilar applications per year, each requiring the
applicant to spend 860 hours compiling the necessary information.
But each notification of a patent dispute will take just two hours.
Meanwhile, five FDA draft guidances covering the 2012 Generic
Drug User Fee Amendments (GDUFA) are now open for comment
until early March after the agency reopened the docket in response
to requests for additional time.
Having first been issued by the FDA last year before a full-day
public hearing on 17 September (Generics bulletin, 5 September 2014,
page 16), the five guidance documents cover: the content and format
of abbreviated new drug applications (ANDAs); refusal to receive
for lack of proper justification of impurity limits; amendments and
easily correctable deficiencies; prior-approval supplements; and
controlled correspondence related to generic-drug development. G
PRICING & REIMBURSEMENT
BGMA urges new approach
R
eviews of payment and reimbursement mechanisms are needed
in the UK to “deliver maximum value and sustain the market”
for generics and biosimilars, according to the British Generic
Manufacturers Association (BGMA). “New thinking is needed if
patients are to benefit from the more complex medicines that generic
manufacturers are increasingly producing,” said BGMA director
general Warwick Smith.
“The traditional generic market in the UK has been enormously
successful, saving the National Health Service (NHS) billions of pounds
annually,” Smith observed. “But we are also seeing the development
of ever more complex medicines which will revolutionise patient
outcomes.” These included biological drugs, Smith said, as well as
“greater incremental innovation” in areas such as delivery systems,
combinations or patient-care packages.
G
PATENT LITIGATION
Lilly keeps up Canada attack
E
li Lilly is maintaining its pursuit of damages from the Canadian
government under the North American Free Trade Agreement
(NAFTA) for “illegal” decisions to invalidate brand patents, despite a
counter-filing from the government backing the decisions. “Nothing
in their filing changes our strongly-held belief that Canada’s improper
invalidation of our patents under its unique and burdensome ‘promise’
utility is inconsistent with Canada’s NAFTA obligations,” the firm
said. Action was initiated in 2013 over decisions to invalidate patents
protecting Lilly’s Strattera (atomoxetine) and Zyprexa (olanzapine)
brands (Generics bulletin, 6 September 2013, page 23).
G
27 February 2015
GPHA ANNUAL MEETING
REGULATORY AFFAIRS
REGULATORY AFFAIRS
M
A
CDER pledges a raft OGD sets targets for
of ‘radical changes’ ANDA action dates
ajor changes on quality – moving away from punishing
manufacturing deficiencies to incentivising industry to adapt a
culture of quality – are underway at the US Food and Drug
Administration (FDA), according to the director of the agency’s
Center for Drug Evaluation and Research (CDER), Janet Woodcock.
Woodcock told delegates to the Annual Meeting of the US Generic
Pharmaceutical Association (GPhA) in Miami, US, this month that
CDER planned to “radically change the way we do things on regulating
quality”. The goal of initiatives such as setting up an Office of
Pharmaceutical Quality (OPQ), coordinating inspections more
effectively and implementing a harmonised information-technology
platform was, she said, to incentivise industry to make high-quality
drugs “without extensive regulatory oversight”.
Bringing together around 1,000 staff in the OPQ would, Woodcock
insisted, give CDER “one quality voice” for generics and brands, and
help the agency move away from “giving out tickets” to performing
surveillance of quality based on metrics and site inspections.
A Program Alignment Group (PAG) was ensuring that CDER was
improving coordination between reviewers and field inspectors within
the FDA’s Office of Regulatory Affairs (ORA), Woodcock noted. And
an information-technology platform was collating in a single repository
information on registered facilities, field reports and inspection history.
“We welcome the agency’s focus on quality, including its work
to enhance inspection protocol,” stated the GPhA’s president and
chief executive officer, Ralph Neas. Applauding the FDA’s “strides
towards process improvements and structural evolution”, Neas expressed
optimism that the agency would start to clear a backlog of around
4,000 abbreviated new drug applications (ANDAs) awaiting approval. G
IN BRIEF
GPhA – the US Generic Pharmaceutical Association – will soon ask
its members to vote on proposed changes to its bylaws that would
enable the association to create a biosimilars division. Acknowledging
that several originators, either alone or through alliances with
generics players, were developing biosimilars, GPhA chairman
Craig Wheeler said the division would have a separate budget and
board. The division’s chair would sit on the full GPhA board, which
would ensure that the division acted consistently within the
association’s broader goals and vision.
GLOBAL GENERICS SALES are approaching US$200 billion
annually, according to IMS Health’s Doug Long. In the 12 months
ended September 2014, turnover grew by 10% to just over US$195
billion. Volume growth was 5% to almost 1.02 trillion standard units.
“The US and ‘pharmerging’ markets generate most of the generics
value sales. The volume growth rate is declining,” Long observed.
EXPRESS SCRIPTS is the winner of the GPhA’s inaugural
Outstanding Partner Recognition. Handing the award to Express
Scripts’ vice-president of government affairs, Jonah Houts, GPhA
president and chief executive officer Ralph Neas described the
pharmacy benefits manager as “one of the staunchest and most
effective allies” the association had. Noting that Express Scripts
handled more than 1 million prescriptions each day, Neas praised the
company for sponsoring research on biosimilars’ savings potential. G
27 February 2015
round 1,000 target action dates (TADs) – internal deadlines for
the US Food and Drug Administration (FDA) to act on pending
abbreviated new drug applications (ANDAs) – are to be assigned by
the end of March this year. “The TADs will be March to September
2015,” stated Kathleen Uhl, who was recently made the permanent
director of the FDA’s Office of Generic Drugs (OGD).
Delivering the keynote address at the 2015 Annual Meeting of
the US Generic Pharmaceutical Association (GPhA) in Miami, US,
Uhl described assigning TADs and notifying applicants as “a work
in progress”, as the agency finalised plans on how to communicate
its plans to industry.
Such TADs, Uhl stressed, applied only to ANDAs, and not to
prior-approval supplements (PASs). Setting such target dates was not
required by the Generic Drug User Fee Act (GDUFA), she explained,
adding that the agency would regard an action as a final or tentative
approval, or as a complete response letter.
Target dates for pre-year-3 ANDAs
Uhl said OGD’s goal was to assign TADs for all ANDAs submitted
before the third year of GDUFA started on 1 October 2014, after
which the agency is to review and act on 60% of original ANDA
submissions within 15 months from the submission date. However,
she said, assigning TADs would occur gradually “and with caveats”
to enable the OGD to “manage inventory and synchronise review
work”, as well as to align review and inspection activities.
While TADs would be based on “workload-management factors”,
the agency would make exceptions for large, first-time generics, Uhl
clarified. For these drugs, it would aim to assign TADs that
corresponded with the patent expiry dates or the earliest possible date
that the FDA could approve each ANDA. Several months before the
TADs for such major first-time generics, the agency would aim to
provide “launch planning updates”, Uhl revealed, although this
remained “a work in progress”.
Acknowledging that TAD was “a made-up term” not found in
legislation, Uhl said the agency would implement target dates without
guidance or a manual of policies and procedures (MAPP). One fixed
date assigned to each ANDA could not be exchanged for another
TAD, she added, not least because such dates were in part dictated by
the OGD’s workload. “We may miss a TAD if we can get an ANDA
to approval in a short amount of time,” she stated.
Acknowledging that the OGD had a backlog of around 3,300
ANDAs pending action – plus another 700 that were with industry
awaiting responses – Uhl admitted that the agency needed to “move
the freight”. At the same time, she pointed out, GDUFA had imposed
fixed targets to act on applications currently being submitted.
During the first two years of GDUFA ended October 2014 – which
had seen 2,441 ANDAs filed, more than the agency had expected –
OGD had moved to White Oak, restructured into a ‘super office’ and
set up an integrated information-technology platform, Uhl explained.
Having exceeded Congressional targets by hiring 952 staff under
GDUFA as of 19 November 2014, the agency was “in a good place”
to meet its commitments, she maintained. Enhanced informationtechnology systems in place from 1 October 2014 were helping the
OGD to coordinate reviews, correspondence, inspections and user fees.
“Your patience, feedback and input during GDUFA implementation
is greatly appreciated,” Uhl told delegates. “We recognise that this
has been difficult, disruptive and painful.”
G
PRODUCT NEWS
BIOLOGICAL DRUGS
RESPIRATORY DRUGS
A
L
Apotex has filgrastim Lupin enlists Celon
accepted in the US for American Advair
potex says it has become the first company to have two biosimilar
filgrastim applications under active review by the US Food and
Drug Administration (FDA) after the Canadian firm’s Grastofil
(filgrastim) biosimilar version of Amgen’s Neupogen brand was
accepted for filing by the agency. This follows quickly on from the
FDA accepting Apotex’ filing for biosimilar pegfilgrastim – equivalent
to the US originator’s US$3 billion Neulasta blockbuster – late last
year (Generics bulletin, 16 January 2015, page 15).
Grastofil was developed through a 2008 North American and
European partnership with India’s Intas Pharmaceuticals that was a year
later extended to cover pegfilgrastim (Generics bulletin, 13 February
2009, page 17). Intas provides the active substance from its plant in
Moraiya, India.
Around 18 months ago, Apotex secured a pan-European centralised
marketing authorisation for Grastofil, and subsequently licensed the
biosimilar to Stada (Generics bulletin, 1 November 2013, page 14).
Noting that it would, like its pegfilgrastim candidate, market
Grastofil in the US through its ApoBiologix business, the Canadian
firm said US sales of Neupogen reached approximately US$1 billion
last year, according to Symphony Health Solutions.
Sandoz’ US biosimilar filgrastim candidate – filed with the FDA
last year (Generics bulletin, 8 August 2014, page 1) – has received
backing from the agency’s Oncologic Drugs Advisory Committee. G
upin has struck an agreement with Polish firm Celon Pharma to
jointly develop a generic version of GlaxoSmithKline’s US$7 billion
Advair Diskus (fluticasone/salmeterol) dry-powder inhaler in the US,
Canada, Mexico and “other key markets”.
Under the agreement, Celon will supply the respiratory-disease
treatment to Lupin, which will, in turn, hold marketing rights. No
financial terms were disclosed.
Vinita Gupta, Lupin’s chief executive officer, maintained that
Celon’s “experience in the development and manufacturing of
fluticasone/salmeterol dry-powder inhalers in Europe”, coupled with
the Indian firm’s “expertise in inhalation-product development and
commercialisation in the US and other markets”, would accelerate
the process of bringing generic Advair Diskus to global markets.
Around a year ago, the Indian firm hired Maurice Chagnaud,
formerly head of Teva’s businesses in central and eastern Europe, to
further its respiratory franchise in the role of president of European
operations and head of inhalation strategy (Generics bulletin, 7 March
2014, page 31). Lupin then appointed Theresa Stevens, who gained
experience in the respiratory arena during a nine-year stint with
Novartis, as chief corporate development officer (Generics bulletin,
2 May 2014, page 27).
Last year, Mylan said it expected to imminently commence
Phase III clinical trials for the first US generic rival to Advair
(Generics bulletin, 3 October 2014, page 19), having acquired the
global rights to develop and market a generic version of the product
from Pfizer three years earlier.
The US generics player plans to file an abbreviated new drug
application (ANDA) for Advair in the third quarter of this year and
introduce the first AB-rated, substitutable generic in 2016.
Meanwhile, Lupin has allied with US-based respiratory specialist
InspiRX to launch in the US the “all new” InspiraChamber anti-static
valved holding chamber (VHC) device. Under the agreement, the Indian
company will gain the exclusive US rights to promote, distribute and
market the product, which is said to provide a more effective delivery
for asthma medicines, particularly for young children and the elderly. G
REGULATORY AFFAIRS
GPhA responds over REMS
C
larity is needed over US Food and Drug Administration (FDA)
draft guidance aimed at helping applicants to obtain samples of
brands governed by a risk evaluation and mitigation strategy (REMS),
according to the US Generic Pharmaceutical Association (GPhA).
Commenting on the recent draft guidance – which describes how
firms can obtain a letter from the FDA stating that bioequivalence study
protocols contain safety protections comparable to reference listed
drug (RLD) protections (Generics bulletin, 16 January 2015, page 9) –
the GPhA said it was concerned that brand companies may still
“use this guidance as another tool to deny or further delay
providing RLD samples”. The agency should therefore specify that
an FDA approval letter is not a legal requirement for a brand
company to supply samples, the GPhA suggested.
The association also recommended a 30-day clock be applied to
FDA reviews of bioequivalence study protocols to help applicants
“plan their development activities”.
G
27 February 2015
PRODUCT NEWS
GASTROINTESTINAL DRUGS
Mylan must wait for
esomeprazole in US
M
ylan has been awarded a tentative approval for its US rivals to
AstraZeneca’s Nexium (esomeprazole) blockbuster, but will
have to wait until paediatric exclusivities associated with two US
patents expire later this year to receive final clearance from the US
Food and Drug Administration (FDA).
According to a letter addressed to Mylan’s senior manager of
regulatory affairs, Shane Shupe, the US firm’s esomeprazole 20mg
and 40mg delayed-release capsules are “safe and effective for use as
recommended in the submitted labelling”, warranting a tentative nod.
But until paediatric exclusivities attached to US patents 5,690,960
and 5,714,504 expire – on 25 May 2015 and 3 August 2015
respectively – the FDA will not grant Mylan final approval.
Nexium is also protected by eight other US patents, but, Mylan
told the FDA, no litigation was brought in response to the company’s
paragraph IV patent challenges to seven of them within the 45-day
window that would have triggered a 30-month stay on approval. An
eighth US patent covers a carved-out indication.
Teva recently became the first company to receive final approval
for generic esomeprazole capsules after the FDA stripped Ranbaxy
of its tentative approval (Generics bulletin, 14 November 2014,
page 20) and, later, the Indian firm’s right to 180-day generic
market exclusivity (Generics bulletin, 6 February 2015, page 17).
Siggi Olafsson, head of Teva’s global generics business, told
investors that the firm would introduce its rival to Nexium this month
into a brand market valued at almost US$2 billion. The launch, he
explained, had been held up by AstraZeneca having changed the
original’s label just before Teva got its approval, requiring Teva to
re-label its version. “There are quite a few applications pending at
the FDA. Of those, quite a few are on 30-month stays,” he noted.
India’s Cipla says it is supplying Teva with both the esomeprazole
active pharmaceutical ingredient and the formulation (see page 2). G
BIOLOGICAL DRUGS
Actavis drops rFSH project
A
ctavis has terminated development of its recombinant folliclestimulating hormone (rFSH) “as part of portfolio rationalisation”.
The firm had licensed the female-infertility treatment from Itero in
2010 (Generics bulletin, 6 August 2010, page 19).
Through an alliance with Amgen, Actavis is developing four
biosimilars. Their ABP980 and ABP215 alternatives to Herceptin
(trastuzumab) and Avastin (bevacizumab) are currently in Phase III
clinical trials, while an ABP798 rival to Rituxan (rituximab) is “clinical
ready”. The firms are at the process-development stage for biosimilar
Erbitux (cetuximab) with their ABP494 project. Actavis is also
independently developing a cell line for a fifth, undisclosed biosimilar.G
KIDNEY DISEASE DRUGS
Teva launches UK sevelamer
T
eva says it is “among the first” to launch a rival to Sanofi’s Renvela
(sevelamer) 800mg tablets in the UK following patent expiry. The
kidney-disease treatment is available in 180-count packs.
G
27 February 2015
IN BRIEF
PAR has received a tentative US Food and Drug Administration
(FDA) nod for a generic rival to Takeda’s Colcrys (colchicine)
0.6mg tablets. The Japanese originator recently lost its bid to have
an injunction placed on Hikma to prevent the Jordanian firm from
launching its 505(b)(2) hybrid colchicine 0.6mg capsules (Generics
bulletin, 6 February 2015, page 20), and subsequently licensed an
authorised generic of Colcrys to Prasco.
EUROFARMA has struck a deal with Melinta Therapeutics in
Brazil to market delafloxacin, “an investigational fluoroquinolone”.
Under the terms of the agreement, Eurofarma will be responsible
for obtaining regulatory approval in Brazil and will be able to
market, sell and distribute the drug for treating acute bacterial skin
and skin-structure infections. Melinta will receive a combined
upfront cash and equity payment of US$15 million, as well as
milestone and royalty payments.
ACTAVIS has sent a paragraph IV notification to Orexo and
Galena Biopharma for generic rivals to the originators’ Abstral
(fentanyl) 0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.6mg and 0.8mg sublingual
tablets. Three US patents, all of which expire on 24 September 2019
and belong to new drug application (NDA) holder Galena, shield
the analgesic. Orexo said it was “working closely with our partner
Galena to review the details of this notice letter”.
CIPLA says it has been awarded its first tender in Germany for the
Indian firm’s salmeterol/fluticasone 25µg/125µg and 25µg/250µg
pressurised metered-dose inhalers (pMDIs), which it markets in
the country under the Serroflo brand name. Having launched in
Germany last year, Cipla also in 2014 rolled out the treatment for
asthma and chronic obstructive pulmonary disease (COPD) in
Sweden, Slovakia, the Czech Republic and Croatia under various
fantasy names (Generics bulletin, 19 September 2014, page 21).
GEDEON RICHTER has agreed to loan US$5 million to US-based
women’s healthcare specialist Evestra to help advance its pipeline
of innovative products into clinical stages.
BERLIN CHEMIE, a subsidiary of Italian firm Menarini, intends
to invest around C10 million (US$11 million) in constructing a
distribution unit next to its existing pharmaceutical facility in the
Kaluga region of Russia. An 80,000 sq m unit – which is to comply
with international good distribution practice (GDP) standards – will
eventually form a “single logistic-production complex” with the
firm’s solid dose facility that was opened two years ago.
SANDOZ has launched US rivals to Boehringer Ingelheim’s
Micardis (telmisartan) 20mg, 40mg and 80mg tablets. Six other
generics players – Actavis, Alembic, Glenmark, Mylan, Torrent and
Zydus Cadila – hold approved abbreviated new drug applications
(ANDAs) for the antihypertensive brand, which had sales of
around US$174 million last year, according to IMS Health data.
FARMAK has expanded its range of nasal products by launching
phenylephrine 10ml nasal drops in Ukraine. Containing 2.5mg
phenylephrine as well as 0.25mg dimetindene, the product – which
is indicated for treating allergic rhinitis, nasal congestion and
otitis – is marketed under the brand name Milt.
SANOFI has sued four companies – Actavis, Apotex, Breckenridge
and Mylan’s Onco Therapies – in a New Jersey district court over
paragraph IV challenges to US patents protecting the originator’s
Jevtana (cabazitaxel) prostate-cancer drug.
G
PRODUCT NEWS
ONCOLOGY DRUGS
BIOLOGICAL DRUGS
C
H
Canada refuses a bar Hospira and Pfenex
on Teva’s bortezomib develop ranibizumab
anada’s Federal Court of Appeal has rejected Janssen’s appeal
against a lower court’s ruling not to bar Teva from obtaining a
Notice of Compliance (NOC), or marketing authorisation, for
bortezomib 3.5mg vials. “Asking a court to prohibit an NOC after
it has issued is like asking someone to close the barn door after the
horses have escaped,” the panel of three judges stated.
Noting that Teva had obtained an NOC for a generic rival to
Janssen’s Velcade in December last year, the appeals judges rejected
the originator’s argument that the Comprehensive Economic and Trade
Agreement (CETA) between Canada and the European Union (EU)
guaranteed it “equivalent and effective rights of appeal”. CETA, the
judges pointed out, was not yet part of Canadian law because it had
not been implemented by statute.
Any conflict arising from Teva having recently filed an abbreviated
new drug submission (ANDS) covering a new route of administration
for bortezomib would have to be addressed by a separate legal
action, the judges added.
G
ONCOLOGY DRUGS
Mylan sued over US Nexavar
M
ylan has been sued in a US district court by Bayer and its partner
Onyx Pharmaceuticals for submitting an abbreviated new drug
application (ANDA) containing a paragraph IV patent challenge for
generic versions of the originators’ Nexavar (sorafenib) 200mg tablets.
Six US patents are listed against Nexavar in the US Food and
Drug Administration’s (FDA’s) Orange Book, the latest of which
expires on 24 December 2027.
Expects 180-day exclusivity
As the first company to file an ANDA containing a paragraph IV
certification, Mylan expects to be eligible for 180-day generic market
exclusivity for the kidney-cancer treatment, which had US sales of
around US$48 million in the 12 months ended 31 December 2014,
according to IMS data. Mylan is partnering with Natco on sorafenib. G
ANTIRETROVIRAL DRUGS
Patent Pool adds raltegravir
M
erck, Sharp and Dohme (MSD) has agreed a deal with the
Medicines Patent Pool that will allow generics firms to “develop,
manufacture and sell low-cost paediatric versions of raltegravir in
countries with the highest burden of disease, where 98% of children
with HIV in the developing world live”.
Greg Perry, the Patent Pool’s executive director, said the group
was “pleased to have MSD on board as a new private-sector partner
working with us on paediatric programmes”. The World Health
Organization (WHO) recommends raltegravir as a component of
paediatric third-line treatment.
“Raltegravir adds to our arsenal of paediatric licences in
supporting better options for children in low- and middle-income
countries,” Perry said, “and can benefit the most neglected subsegment: infants and toddlers less than three years of age.”
G
ospira and Pfenex have struck a deal to develop a biosimilar rival
to Genentech’s Lucentis (ranibizumab) that the two firms will
“commercialise for worldwide sales”.
Under the terms of the deal, Pfenex will receive an upfront payment
of US$51 million once the collaboration receives antitrust approval.
Over the following five years, the firm will be eligible to receive “a
combination of development and sales-based milestone payments up
to an additional US$291 million”, as well as a “tiered double-digit
royalty on net sales of the product”.
Noting that Lucentis had global sales of around US$4 billion in
2014, Hospira said it would share Phase III equivalence clinical-trial
costs with Pfenex, while Hospira would be responsible for
manufacturing and selling the product worldwide. An executive
steering committee comprised of equal representation from the two
firms will govern the collaboration, which includes an option for future
alliances on other products.
Pfenex’ ranibizumab candidate, ‘PF582’, is currently undergoing
Phase Ib/IIa safety and tolerability trials, with secondary objectives
that include comparative pharmacokinetic and pharmacodynamic
evaluations to help demonstrate biosimilarity to Lucentis.
The ophthalmic biosimilar would “expand Hospira’s biosimilars
pipeline to include a new therapeutic area”, observed the firm’s chief
scientific officer, Sumant Ramachandra. Bertrand Liang, Pfenex’ chief
executive officer, said the deal “further validates the productdevelopment strength and capability of Pfenex as we continue to
advance our pipeline”.
G
BIOLOGICAL DRUGS
US court sets filgrastim date
A
California district court has set 2 March as the date on which it
will hear Amgen’s motion for a preliminary injunction to prevent
Sandoz from marketing a rival to its Neupogen (filgrastim) original
in the US. Amgen alleges that Sandoz has failed to follow statutory
requirements for handling patent disputes, but the biosimilar applicant
insists it can elect not to disclose details of its application and
manufacturing practice. Last month, an advisory committee
recommended that the US Food and Drug Administration (FDA)
approve Sandoz’ Zarxio (filgrastim) biosimilar with all the same
indications as Neupogen.
G
WEIGHT-LOSS TREATMENTS/ANALGESICS
TWi US takes two from Teva
T
Wi Pharmaceuticals has announced that its US rivals to Megace ES
(megestrol) 625mg/5ml and Lidoderm (lidocaine) 5% patches will
be marketed by the Taiwanese company’s US subsidiary, rather than
Teva as originally planned, following an agreement with Teva.
“TWi has assembled a sales and distribution team in the US and
plans to launch several products in the US under TWi’s label this year,”
the firm revealed. This meant that TWi would be able to “enjoy all
the profits derived from the products”, said TWi’s president, Calvin
Chen. “This is consistent with the company’s strategy.”
G
27 February 2015
PRODUCT NEWS
BIOLOGICAL DRUGS
ANTIRETROVIRALS
C
A
Celltrion and Hospira Lupin wins an appeal
gear up for infliximab on US Trizivir patent
elltrion and Hospira prepared to launch their Remsima and
Inflectra biosimilar rivals to Janssen’s Remicade (infliximab) in
Europe by unveiling their latest data and research at the 10th annual
congress of the European Crohn’s and Colitis Organisation (ECCO).
South Korea’s Celltrion – which launched Remsima in several
European markets through local partners on 25 February (see page 26)
– revealed a study suggesting that its Remsima monoclonal antibody
could reduce the cost of treating Crohn’s disease in France, Italy and
the UK by up to C336 million (US$380 million) over five years. “These
cost savings could help improve patient access to life-changing
treatments,” the company argued.
Presenting the study as a poster in Barcelona, Spain, Celltrion
said three pricing scenarios produced savings between 2015 and 2019
across the three countries ranging from C76 million to C336 million.
This calculation was based on discounts of 10%, 20% and 30% to
the originator brand, which was assumed to maintain the same price
following the entry of biosimilar competition.
“Market-uptake growth was also varied in each of the scenarios
at 20%, 30%, and 40%, respectively. The market share was assumed to
be 25% in the first year in all scenarios,” Celltrion noted, adding that
it had calculated the number of patients eligible for infliximab
treatment based on the prevalence of Crohn’s disease, total population
and annual population growth in France, Italy and the UK.
Furthermore, the South Korean company presented six posters
on clinical experience with biosimilar infliximab during the ECCO
congress. These covered 332 patients, including children, with
inflammatory bowel disease (IBD). “The safety and efficacy of
biosimilar infliximab in rheumatoid arthritis and ankylosing spondylitis
have previously been demonstrated in two pivotal clinical trials, Planetas
and Planetra,” the company pointed out.
Three infusions reduce disease activity
During a satellite symposium session, Jørgen Jahnsen, Professor of
Gastroenterology at the University of Oslo in Norway, presented
evidence of a reduction in disease activity at week 14 in 74 IBD
patients following three infusions of biosimilar infliximab.
Celltrion’s president, Stanley Hong, said the data presented at
the ECCO congress supported the decision made by the European
Medicines Agency (EMA) to approve Remsima and Inflectra for
treating IBD based on extrapolating data from the Planetas and
Planetra rheumatology trials. “We are conducting prospective
observational and registry trials as part of pharmacovigilance in the
European Union (EU) and South Korea to monitor the safety of
biosimilar infliximab,” he noted.
Hospira highlighted a poster presented during the same congress
by Hungarian clinicians that detailed interim results from a nationwide
observational cohort started after biosimilar infliximab entered the
Hungarian market in May 2014. “For the first 90 patients – 57 with
Crohn’s disease and 33 with ulcerative colitis – treated with Inflectra,”
Hospira observed, “reductions compared with baseline were seen in
validated measures of disease activity after both two and six weeks
of treatment.”
“Results show a comparable response in patients treated with
Inflectra to that expected with the reference product, Remicade,” Hospira
stressed, adding that the independent Hungarian study would continue
to enrol patients whom it would follow for 108 weeks for those with
Crohn’s disease and for 54 weeks for those with ulcerative colitis. G
27 February 2015
district-court victory won by Lupin over a US patent protecting
Trizivir (abacavir/lamivudine/zidovudine) until March 2016
has been upheld without comment by a panel of three US Court of
Appeals judges.
Lupin had at the end of 2013 convinced a Delaware district court
that its generic version of Trizivir did not infringe Viiv Healthcare’s
US patent 6,417,191. The same court found that the ‘191 patent was
not invalid. Teva had already admitted that its ANDA for a rival to
Epzicom (abacavir/lamivudine) infringed the patent (Generics
bulletin, 10 January 2014, page 19).
Delaware District Judge Richard Andrews ruled that Lupin’s use
of the abacavir sulfate salt put its generic outside the scope of a key
tablet formulation claim in the ‘191 patent that covered pure or ‘free
base’ abacavir. “The patentee differentiated between the pure, or free
base, form of abacavir and the salt form in the claims themselves,
undermining the argument that the salt form is intrinsically
encompassed by the free base of pure form,” Andrews stated.
Teva had stipulated to infringement under the Delaware court’s
claim construction. The Israeli firm, along with Lupin, failed in its
obviousness attack on the ‘191 patent.
G
MULTIPLE SCLEROSIS DRUGS
BioIntegrator sued on Gilenya
N
ovartis has filed a suit against Russia’s BioIntegrator in a Moscow
arbitration court, following the firm securing a Russian registration
for its Nescler (fingolimod) generic rival to the originator’s Gilenya
0.5mg capsules in November last year.
The Switzerland-based originator demanded that the registration
for the multiple-sclerosis drug be deemed invalid as it “has reasonable
grounds to suspect” that the Russian company had infringed six-year
data exclusivity for Gilenya – which was registered in Russia on 17
August 2010 – while establishing bioequivalence between the two drugs.
Meanwhile, BioIntegrator has responded by claiming that it had
“all legal grounds” for registering Nescler, the bioequivalence of which
had been proven though comparative pre-clinical and clinical trials.
The Russian company also said that its registration was filed before
such legislation on data protection came into force in Russia. Moreover,
it added, fingolimod “has never been patented in Russia”.
At Novartis’ request, the court has ordered the Russian Ministry
of Health to present the Nescler dossier at a hearing on 11 March. G
BIOLOGICAL DRUGS
Oncobiologics meets endpoints
O
ncobiologics says its ONS-3010 potential biosimilar rival to
AbbVie’s Humira (adalimumab) “met the primary endpoints in
its first clinical study”. A three-arm, single-dose pharmacokinetic
study in healthy volunteers that was conducted in Leiden, the
Netherlands, produced endpoints that “met the bioequivalency criteria
of geometric mean ratios within a 90% confidence interval of 80%125%”. An exploratory ex vivo pharmacodynamic study “showed
encouraging results”, the US developer said.
G
PRODUCT NEWS
RESPIRATORY DRUGS
EPILEPSY DRUGS
A
A
Actavis has to halt Pregabalin dispute
budesonide in the US will persist in the UK
ctavis has been forced to halt distribution of its generic rival to
AstraZeneca’s Pulmicort Respules (budesonide) inhalation
suspension in the US. The Court of Appeals has issued a temporary
injunction preventing further distribution of the paediatric respiratory
drug pending a hearing on the originator’s appeal against a New Jersey
district court’s finding that AstraZeneca’s US patent 7,524,834 was
invalid due to obviousness.
“The temporary injunction does not address product shipped prior
to its issuance,” Actavis pointed out. On 13 February, immediately upon
the New Jersey court’s obviousness ruling, Actavis had announced its
launch of the 0.25mg and 0.5mg vials for which it had held final
approval for two-and-a-half years, but had been unable to market due
to an injunction obtained by AstraZeneca. The New Jersey ruling
lifted the previous injunction.
In April 2013, the New Jersey court had found that generic
defendants Actavis, Apotex and Sandoz did not infringe the ‘834 patent,
while AstraZeneca’s US patent 6,598,603 was invalid (Generics bulletin,
5 April 2013, page 12). But a few months later, the US Court of Appeals
reversed and remanded the non-infringement finding on the ‘834
patent, which expires on 11 May 2019, including a six-month paediatric
extension (Generics bulletin, 15 November 2013, page 19).
Ruling in light of the Court of Appeals’ construction of the term
‘micronised powder composition’, New Jersey District Judge Renée
Marie Bumb said prior art rendered the ‘834 patent invalid. “Evidence
clearly and convincingly demonstrates that a person of skill in the
art would have had a reasonable expectation of successfully preparing
the claimed sterile budesonide compositions using four of the five
conventional sterilisation techniques,” she decided, ordering a trial to
be held to determine damages. AstraZeneca immediately appealed.
Actavis and Sandoz currently hold US approvals for generic
versions of the paediatric asthma remedy, as does Teva, which has
marketed a generic since late 2009 under the terms of a patent-litigation
settlement reached between the Israeli firm and AstraZeneca the
previous year (Generics bulletin, 5 December 2008, page 19).
AstraZeneca reported US Pulmicort sales down by 6% to US$211
million last year. Actavis said combined brand and generic sales of
budesonide suspension totalled around US$1.1 billion in the year
ended June 2014.
Meanwhile, Actavis has agreed to sell the rights to its US branded
respiratory business to AstraZeneca for an initial US$600 million plus
“low single-digit royalties above a certain revenue threshold”. Actavis
insisted the transaction would “have no impact” on its commitment
to developing generic respiratory drugs.
Actavis will sell the US and Canadian development and
commercial rights to Tudorza Pressair (aclidinium bromide) and
Daliresp (roflumilast) treatments for chronic obstructive pulmonary
disease (COPD), along similar rights to its investigational ‘LAS40464’
aclidinium/formoterol combination that is approved in the European
Union (EU) under the Duaklir Genuair name.
The deal includes AstraZeneca paying Actavis – which gained
the respiratory franchise through its US$28 billion deal for Forest
Laboratories last year (Generics bulletin, 7 March 2014, page 1) –
an additional US$100 million, linked to Actavis agreeing to amend
existing collaborations between the two companies.
Actavis said selling the respiratory brands would allow it to focus
on core therapeutic areas, pay off debt and “invest in further expansion
through business development”.
G
UK legal battle between Actavis and Pfizer over a pregabalin
method-of-use patent is set to continue after Justice Richard Arnold
refused Actavis’ motion for summary judgement and for Pfizer’s
infringement allegation to be struck out. Arnold also allowed Pfizer
to amend its infringement stance to plead a case of subjective intention,
even though the disclosure that the originator was likely to seek from
Actavis could “amount to a fishing expedition”.
Arnold – who recently refused to grant Pfizer an interim
injunction preventing Actavis from offering its Lecaent (pregabalin)
branded generic for indications not covered by Pfizer’s pain methodof-use patent (Generics bulletin, 6 February 2015, page 22) – was
not convinced that Pfizer had presented “reasonable grounds” for
Actavis having subjective intention to infringe. But he could be wrong
in “a developing area of the law”, so facts should be established at trial.
“The issue is one which is likely to be suitable for consideration
not merely by the Court of Appeal, but also by the Supreme Court,”
Arnold commented.
Actavis has just launched Lecaent in eight strengths with list
prices of £57.96 (US$89.82) for 56 capsules, and £86.94 for 84.
Addressing a recent finding by Hague Court of Appeal that Sun
Pharma had infringed a second medical-use patent protecting Novartis
Aclasta (zoledronic acid) brand (Generics bulletin, 6 February 2015,
page 22), Arnold noted that the Dutch court had held that Sun “had
the requisite knowledge” that supplying its version via a tender was
likely to infringe indirectly Novartis’ osteoporosis method-of-use
patent. “The court took into account the fact that Sun had not taken
steps which it could have taken,” he added.
Arnold agreed with Actavis that Pfizer had ignored the steps the
generics firm had, and would, take to avoid its Bulgarian-made Lecaent
capsules from being prescribed for the patented pain indication. In
any case, he said, Pfizer had not alleged intent on the part of Actavis,
merely that third-party infringement was “a foreseeable consequence”
of having carved out the patented indication from the generic’s label.
“Actavis contends that these allegations ignore the fact that the nonpain market is very substantial,” Arnold remarked, adding that Pfizer
accepted that Consilient Health had avoided infringement by carving
out the patented indication from labelling for its Rewisca pregabalin
capsules. Dr Reddy’s has adopted a similar approach for the Alzain
branded generic for which it has just secured UK approval.
G
BIOLOGICAL DRUGS
Biocad rivals Russian Avastin
B
iocad expects to launch its Russian rival to Roche’s Avastin
(bevacizumab) monoclonal antibody in the second half of 2015,
having recently submitted its registration dossier for the drug to the
country’s Ministry of Health. The Russian company claims that its
metastatic-cancer treatment – in which the firm has invested
US$10 million – is the first domestic bevacizumab and “does not
differ in efficacy and safety compared to the original drug”.
Pointing out that the Russian government and patients spent a
total of RUB3.2 billion (US$48 million) on imported branded
bevacizumab last year, Biocad’s vice-president, Roman Ivanov,
anticipated that with its “significantly cheaper” alternative, the firm
would “fully meet patients’ demand” for the drug.
G
27 February 2015
PRODUCT NEWS
ANALGESICS/ATTENTION DEFICIT HYPERACTIVITY DISORDER DRUGS
BIOLOGICAL DRUGS
M
K
Mayne pays US$16m Spain’s Kern Pharma
to control two in US introduces infliximab
ayne Pharma has agreed to pay up to US$15.7 million in total
to take full control of two US generics – methamphetamine
tablets and triple-dose combination butalbital/acetaminophen/caffeine
(BAC) capsules – that the Australian firm currently markets
through local partnerships. Methamphetamine is distributed by Mylan,
while Libertas Pharma markets the BAC combination.
While both products are currently marketed under a profit-sharing
scheme, Mayne will through the deal acquire “full ownership” of both
generics, including manufacture, distribution and sales control. The
agreement for methamphetamine is due to close on 5 March, while
the BAC deal is expected to follow by June. Mayne plans to bring
methamphetamine distribution in-house from April.
Pointing out that the market for both products was “attractive with
limited generic competition”, Mayne said the two products – for which
the company is US market leader – were expected to add around
US$3.5 million annually to its earnings before interest, tax, depreciation
and amortisation (EBITDA).
Meanwhile, Mayne has agreed to buy the US rights to the Doryx
(doxycycline) acne treatment brand and “related assets” from Actavis
for US$50 million.
The transaction is set to close by the end of February, but Actavis –
which had gained the rights to the Doryx brand through its acquisition
of Mayne’s Doryx partner, Warner Chilcott, in 2013 – will continue
to distribute Doryx 75mg, 100mg and 150mg delayed-release tablets
in the US for a transition period lasting until 2 May this year.
To support the implementation of Doryx, Mayne has announced
plans to establish a dedicated US Specialty Brands division that
will include 66 sales representatives.
G
BIOLOGICAL DRUGS
Mabion eyes Latin rituximab
P
olish firm Mabion says it has filed a registration dossier for its
rival to Roche’s MabThera (rituximab) monoclonal antibody in
Argentina. At present, the firm has submitted pre-clinical analysis
and studies for its MabionCD20 version of the cancer and rheumatoidarthritis treatment to the country’s Ministry of Health while it completes
Phase III clinical trials. The company said it intended – in collaboration
with its Argentine partner LKM – to seek further marketing
authorisations for the drug in other Latin American countries, including
Bolivia, Chile, Colombia, Ecuador, Paraguay, Uruguay and Venezuela.G
OPHTHALMIC DRUGS
Lupin gets US bimatoprost nod
L
upin has received final US Food and Drug Administration (FDA)
approval for its generic version of Allergan’s Lumigan (bimatoprost)
0.03% ophthalmic solution which the US originator discontinued in
2012. The Indian firm says it intends to introduce the treatment for
elevated intraocular pressure in patients with open angle glaucoma or
ocular hypertension in the US “shortly”. Generics players Apotex and
Sandoz currently hold tentative US nods for bimatoprost 0.03%
ophthalmic solution.
G
27 February 2015
ern Pharma says it has become the first Spanish company to
market a biosimilar monoclonal antibody by introducing infliximab
in mid-February through a local alliance with South Korea’s Celltrion
Healthcare. The Spanish firm is distributing the Remsima antiinflammatory agent through its newly-created Kern Pharma Biologics
biosimilars unit (Generics bulletin, 6 February 2015, page 18).
To ensure full traceability, Remsima features an adhesive label
on the vial, as well as a 2D data matrix on cartons and 100mg vials
that details the batch number and expiration date.
“This launch marks the first in a long list of biosimilar products
and, therefore, the start of a development project which is one of the
most important and strategic branches of the company in the coming
years,” stated Kern’s director, Raúl Díaz-Varela. “The goal is to expand
our biosimilars portfolio through Celltrion,” he said, adding that
this formed part of a growth and diversification strategy of offering
added-value products.
Kern cited data from Spain’s generics industry association, Aeseg,
suggesting biosimilars could generate savings of C1.50 billion (US$1.70
billion) by 2020 (Generics bulletin, 21 March 2014, page 13).
Celltrion has held a centralised European authorisation for
Remsima since September 2013, but paediatric extensions to
supplementary protection certificates (SPCs) protecting the reference
brand, Janssen/MSD’s Remicade, have only just expired in many of
Europe’s largest markets.
Network of alliances in Europe
The deal with Kern in Spain forms part of a network of national
and regional alliances that the South Korean firm has struck for
Remsima in Europe. In the Nordic region, Orion already markets the
drug (see pages 12 and 29), while Hungary’s Egis holds rights in
central and eastern Europe, including the Commonwealth of
Independent States (CIS). Under the terms of a deal reached last year
(Generics bulletin, 5 September 2014, page 22), Mundipharma
secured rights to market the biosimilar upon SPC expiry in Belgium,
Germany, Italy, Luxembourg and the Netherlands, as well as in the
UK, where an SPC extension ran until 24 February.
G
MULTIPLE SCLEROSIS DRUGS
Eight are sued on US Ampyra
E
ight generics firms have been sued by Acorda Therapeutics for
filing paragraph IV patent challenges for generic versions of
the originator’s Ampyra (dalfampridine) 10mg extended-release
tablets. Acorda’s action has triggered 30-month stays of final US
Food and Drug Administration (FDA) approval for the multiple
sclerosis treatment, which had sales of US$366 million last year.
Five US patents currently protect Ampyra, the latest of which
expires on 26 May 2027. Actavis was last year sued by Acorda for
sending the originator a paragraph IV patent challenge for generic
versions of Ampyra (Generics bulletin, 5 September 2014, page 23).
Meanwhile, Acorda said it would oppose an inter partes review
(IPR) petition a hedge fund had recently filed with the US Patent and
Trademark Office (USPTO) that challenges one of Ampyra’s five US
patents. The 30-month stay on the infringement lawsuits against the
eight ANDA filers would not be impacted by the IPR, Acorda noted. G
PRODUCT NEWS
IN BRIEF
ACTAVIS intends shortly to launch rivals to Reckitt Benckiser’s
Subutex (buprenorphine) 2mg and 8mg sublingual tablets following
final US Food and Drug Administration (FDA) approval. The
treatment for opioid dependence – which saw its first rival from
Roxane in 2009 (Generics bulletin, 30 October 2009, page 17) and
has since been joined by generic versions offered by Teva’s Barr
and Akorn’s Hi-Tech Pharmacal – had branded sales of around
US$108 million last year, according to IMS Health data. Two years
ago, Actavis, along with Amneal, launched the sublingual tablet
formulation of Reckitt’s buprenorphine/naloxone combination,
Suboxone (Generics bulletin, 8 March 2013, page 16).
INTAS says its Accofil (filgrastim) biosimilar rival to Amgen’s
Neupogen original has won “two prestigious tenders”, in the
Netherlands and the UK. Having recently rolled out Accofil pre-filled
syringes in two strengths – 30MU/0.5ml and 48MU/0.5ml – through
its Accord Healthcare subsidiary (Generics bulletin, 6 February 2015,
page 23), Intas said at the time that the biosimilar would initially
be available in the Netherlands, followed by the UK and Poland.
ENDO and its partner BioDelivery Sciences International (BDSI)
have had their new drug application (NDA) for Belbuca
(buprenorphine) buccal film accepted for filing by the US Food
and Drug Administration (FDA). Having been awarded a standard
review by the agency, the treatment for severe pain will, Endo
expects, be reviewed by the agency by October this year.
STRIDES ARCOLAB has reached an agreement with Gilead Sciences
for a licence to the originator’s investigational tenofovir alafenamide
(TAF), both “as a single-agent product and in combination with
other drugs”, in 112 countries. The agreement also provides for a
technology transfer from Gilead to enable the production of “lowcost versions” of the antiretroviral, pending US Food and Drug
Administration (FDA) approval of the product.
MYLAN has received US Food and Drug Administration (FDA)
approval for its memantine 5mg and 10mg tablets. The nod makes
it the first generic to be listed by the FDA as a rival to the Namenda
brand marketed by Actavis’ Forest Laboratories.
RUSSIAN manufacturers will produce 12 pharmaceutical substances
including caspofungin, deferasirox and lenalidomide by 2016 as part
of the country’s Pharma 2020 strategy aimed at developing domestic
alternatives to imported brands. In total, the Russian government is
providing RUB4.45 billion (US$67.3 million) to support the domestic
pharma companies in producing a total of 22 pharmaceutical
substances, including 10 that had previously been announced.
OHIO attorney general Mike DeWine has written to Amphastar’s
chief executive officer, Jack Zhang, requesting rebates for certain
consumers – including police departments – following “dramatic”
price increases for the US firm’s generic naloxone that is used to
treat narcotics overdose. Pointing to an agreement reached with New
York attorney general Eric Schneiderman that allows for a US$6.00
rebate for naloxone distributors, DeWine said a “similar agreement”
would make a “tremendous difference” in Ohio.
CIPLA has won a US$189 million share of a Global Fund
antiretroviral tender. The contract – which runs from the start of
this year until the end of 2017 – covers supplies that will begin in
the near future. The Indian firm said the deal “offers us a great
opportunity to make HIV and AIDS treatment accessible to more
than 140 countries”.
G
BIOLOGICAL DRUGS
Momenta is open to
options on abatacept
M
omenta Pharmaceuticals plans to open negotiations with potential
partners for its M834 biosimilar rival to Bristol Myers-Squibb’s
Orencia (abatacept), as well as for six undisclosed early-stage biosimilar
candidates, after Baxter chose to limit the two firms’ collaboration
to an alternative to Humira (adalimumab).
On 14 February, Baxter’s right to select three biological originals
to target for biosimilar development expired without being exercised.
A couple of days later, Baxter told Momenta it was terminating
collaboration on abatacept for automimmune and inflammatory diseases
such as rheumatoid arthritis under a deal struck three years ago
Follows Baxter pipeline review
Noting that Baxter had been undertaking restructuring and a
pipeline review, Momenta’s president and chief executive officer,
Craig Wheeler, stated: “Our collaboration with Baxter on M923,
biosimilar Humira, remains strong, and we look forward to discussions
in 2015 with potential new partners for M834, a biosimilar version
of Orencia, and our additional biosimilar programmes.”
Wheeler said Momenta – which had cash and marketable
securities totalling US$192 million at the end of last year – would
prefer to strike deals across a portfolio of biosimilars, rather than reach
agreements for individual molecules, as it would simplify investments
in areas such as manufacturing.
“There is a very attractive partnering environment out there,” he
insisted, adding that Pfizer’s prospective takeover of Hospira (see cover)
“raises the stakes for people who want to compete in this game”.
“Orencia is a complex infusion protein which plays to our strength,
and as of now there are few competitors in the hunt,” Wheeler said.
“We are conducting the necessary pre-clinical and process-development
work to advance to the clinic in 2016.”
Baxter was aiming to enrol around 300 healthy volunteers across
three sites in the UK for a single-dose pharmacokinetic study for the
M923 adalimumab candidate, Wheeler said. With an interim safety
analysis for a larger patient study planned, Baxter was targeting
regulatory submissions from 2017.
G
ANTICOAGULANTS
Aspen adds an anticoagulant
A
spen has further bolstered its anticoagulants portfolio by agreeing
to acquire the rights to Novartis’ Mono-Embolex (certoparin
sodium) injectable for US$142 million. The transaction is subject to
German competition authorities’ approval.
As a heparin-based anticoagulant, Aspen pointed out, MonoEmbolex was in the same therapeutic category as its Arixtra
(fondaparinux) and Fraxiparine (nadroparin) injectables that it bought
from GlaxoSmithKline for £700 million (US$1.08 billion) two years
ago (Generics bulletin, 28 June 2013, page 5). But the brand offered
the advantage of weight-independent dosing.
The South African group noted the drug – which had sales of
C68 million (US$77.9 million) in 2013 – was currently only marketed
in Austria, Germany and Switzerland. However, Aspen insisted that
this “presented an opportunity” for the firm to launch the MonoEmbolex brand in other countries.
G
27 February 2015
PIPELINE WATCH
Remicade expiries open options in Europe
F
ebruary brought the expiry of six-month paediatric extensions to
supplementary protection certificates (SPCs) for Janssen’s
blockbuster monoclonal antibody Remicade (infliximab) in some of
Europe’s largest markets, including France, Germany and the UK (see
Figure 1). Hospira seized immediately on the end of SPCs linked to
European patent EP0,610,201 to launch in several countries its
biosimilar infliximab, Inflectra, that it developed with South Korea’s
Celltrion (see front page).
January and February also brought initial SPC expiries for Amgen’s
Enbrel (etanercept). These SPCs were linked to European patents
EP0,464,533 and EP0,471,701. “The Portuguese equivalent of ‘533
has been extended by a six-month paediatric extension until August
2015,” notes Ark Patent Intelligence, which monitors patent, SPC
and data exclusivity durations. In several countries, SPCs linked to
other patents have been granted six-month paediatric extensions, but
all SPCs have expired in Norway and Switzerland.
The European Medicines Agency (EMA) recently accepted for
review an application for biosimilar etanercept submitted by Samsung
Bioepis (Generics bulletin, 6 February 2015, page 18).
In terms of data exclusivity (see Figure 2), January brought the
end of 10 years of data and market exclusivity for Roche’s Avastin
(bevacizumab). An eight-year data exclusivity period for Novartis’
Lucentis (ranibizumab) has also just ended, to be followed by a twoyear market exclusivity period. Ark notes that both molecules share
a common patent family that forms the basis of SPCs running until
December 2019 for bevacizumab and January 2022 for ranibizumab. G
SPC expiries in January/February
Data exclusivity expiries in January/February
INN
Country
January
Etanercept
Ireland, Sweden, Switzerland, UK
Gadobutrol
Belgium, Greece, Hungary, Sweden
Levosimendan
Austria, Greece, Italy, Luxembourg, Sweden
Palifermin
Austria, Belgium, Denmark, France, Germany,
Italy, Luxembourg, Netherlands, Spain,
Sweden, Switzerland, UK
Sevelamer
Greece, Ireland, Italy, Luxembourg,
Netherlands, Portugal, Spain, Sweden, UK
Trastuzumab
Greece
February
Corifollitropin alfa
Italy, Luxembourg, Netherlands, Spain,
Sweden, UK
Desogestrel
Portugal
Drospirenone/EE
Sweden
Efavirenz
Czech Republic
Emtricitabine
Slovenia
Etanercept
Greece, Italy, Luxembourg, Netherlands,
Norway, Spain
Fluticasone/Salmeterol Cyprus
Infliximab
Austria*, Belgium*, Denmark*, France*,
Germany*, Italy*, Luxembourg*, Netherlands*,
Spain*, Sweden*, UK*
Nesiritide
Switzerland
Paliperidone
Portugal
Rizatriptan
Czech Republic
* indicates expiry of paediatric extension to the SPC
Figure 1: Molecules for which supplementary protection certificates (SPCs) expire in
key markets during January and February 2015 (Source – Ark Patent Intelligence)
INN
January
Amlodipine/Valsartan
Bevacizumab
Bortezomib
Certolizumab pegol
Deslorelin
Eculizumab
Fampridine
Liraglutide
Metformin/Linagliptin
Pemetrexed
Ranibizumab
Trilostane
Country/Region
European Union**
European Union
Switzerland
Australia
Belgium, France, Germany, Italy, Luxembourg,
Netherlands, Sweden, UK
Canada*
US
US
US
Switzerland
European Union**
Canada*
February
Clodronic acid
Switzerland
Darunavir
European Union**
Degarelix
Australia
Desvenlafaxine
Canada*
Emtricitabine/Tenofovir European Union
Eplerenone
Canada*
Lisdexamfetamine
Canada*
Nitisinone
European Union
Rasagiline
European Union
Romiplostim
Canada*
Treprostinil
European Union
Velaglucerase alfa
US
Ziconotide
European Union
* This will be followed by a no-marketing period of two years during which a notice of
compliance will not be granted to a generic manufacturer. In addition, a further six months
data protection will be added to the 8-year term for studies of desvenlafaxine, eculizumab,
eplerenone, lisdexamfetamine, romiplostim and trilostane in paediatric populations.
** This will be followed by a no-marketing period of two years during which a generic
may not enter the market in the European Union.
Figure 2: Molecules for which data exclusivity expires in key markets during
January and February 2015 (Source – Ark Patent Intelligence)
This monthly update of key patent, SPC and data exclusivity data is extracted from Ark Patent Intelligence Expiry Database. Covering 50
countries and over 1,600 INNs, Ark Expiry Database contains watertight data teamed with the ultimate in generic launch analysis.
For further information, visit www.arkpatentintelligence.com, or contact:
Europe: +44 870 879 0081. North America: +1 704 665 1986.
Or e-mail: hello@arkpatentintelligence.com.
27 February 2015
PRODUCT NEWS
HEPATITIS C DRUGS
BIOLOGICAL DRUGS
M
N
Doctors challenge
Norway enjoys steep
EU sofosbuvir patent infliximab price cut
ONCOLOGY DRUGS
Eagle strikes deal with Teva
E
agle Pharmaceuticals has licensed its EP-3102 rapid-infusion
alternative to Treanda (bendamustine) to the injectable oncology
brand’s owner, Teva, in a deal worth up to US$120 million. Treanda
had sales of US$767 million last year, Teva reported (see page 4).
Under the exclusive US licence, Teva will waive its orphan-drug
exclusivities for chronic lymphocytic leukaemia (CLL) and non-Hodgkin
lymphoma (NHL) to accelerate EP-3102’s market entry. Eagle – which
has just submitted a new drug application (NDA) and requested priority
review by the US Food and Drug Administration (FDA) – believes
its ready-to-dilute, rapid-infusion 50ml formulation may qualify for
seven-year orphan exclusivities for both CLL and NHL.
Teva will pay Eagle an initial US$30 million, and up to US$90
million in additional milestone payments. Moreover, the US firm will
receive unspecified double-digit royalties on future sales by Teva.
The Israeli firm will be responsible for promoting and distributing
EP-3102 – which was recently found by a clinical trial to be
bioequivalent to the original, but able to be administered more quickly
(Generics bulletin, 16 January 2015, page 8) – while the US company
will be in charge of regulatory approvals, conducting post-approval
clinical studies and initial supply to Teva.
Eagle already holds tentative FDA approval for a 505(b)(2) hybrid
NDA for a 100mg/4ml liquid formulation of Treanda (Generics bulletin,
1 November 2013, page 17). But Teva’s orphan-drug exclusivity blocks
approval for that formulation until September this year. Eagle is also
one of several defendants in a case over Teva’s US Treanda patent
8,791,270 that will be heard by a Delaware district court. Litigation
over US patent 8,445,524 was dismissed.
Meanwhile, Teva has begun shipping US generic rivals to Sanofi’s
Lovenox (enoxaparin) and Pfizer’s Zyvox (linezolid) injectables.
The Israeli firm – which has partnered with Chemi to develop and
manufacture enoxaparin – had been waiting to launch its Lovenox
rivals since receiving final US Food and Drug Administration (FDA)
approval for the anticoagulant in seven strengths last year (Generics
bulletin, 11 July 2014, page 24).
G
orway will be able to procure a biosimilar version of infliximab
at a 72% discount to the existing brand price, according to the
results of a tender announced by local procurement organisation LIS.
Orion offered Remsima at a 72% discount to the current price for
Remicade, and a 69% discount to the lowest price offer made by
Merck, Sharp and Dohme for the brand version as part of the tender.
LIS said Orion had offered Remsima for treating rheumatoid
arthritis at a cost of NOK26,011 (US$3,418) per patient for a course
of treatment, compared to an offer of NOK41,244 for Hospira’s Inflectra
and NOK83,438 for Remicade.
Saves NOK57,000 per patient
Choosing Remsima over Remicade would therefore save
NOK57,427 per patient, LIS pointed out (see Figure 1).
For treating ankylosing spondylitis, Crohn’s syndrome, psoriasis,
psoriatic arthritis and ulcerative colitis, the procurement cost of
Remsima was NOK43,352, compared to NOK68,740 for Inflectra and
NOK139,063 for Remicade. This would save NOK95,711 per patient.G
140
130
120
110
Remsima
Remicade
100
NOK (thousands)
edical charity Doctors of the World has filed an opposition against
a European patent protecting Gilead’s Sovaldi (sofosbuvir)
hepatitis C treatment. The opposition against the EP2,203,462 patent
submitted to the European Patent Office (EPO) puts forward several
grounds of objection, including lack of novelty and inventive step.
“This is the first time any medical organisation has challenged
a drug patent in Europe,” the charity claimed. Citing “the exorbitant
price” of £33,000 (US$50,735) per course of treatment with Sovaldi
in the UK – and a similar price in France – the charity said “generic
versions of sofosbuvir can be produced for as little as £66”. Within the
European Union (EU), it added, 7.3-8.8 million people were estimated
to be infected with hepatitis C, but “several hundred thousand
individuals” were being denied access due to the price.
The ‘462 patent, Doctors of the World alleged, was “clearly aimed
at reserving an unexplored field of research, instead of protecting
factual results of successful research”.
On 20 February, Mylan, Polpharma and Teva each filed oppositions
to the ‘462 patent with the EPO.
G
70
60
57,427
savings
43,352
50
40
30
95,711
savings
83,438
90
80
139,063
26,011
20
10
0
Rheumatoid arthritis
Ulcerative colitis
Figure 1: Price offers submitted to LIS for a course of treatment of Orion’s
Remsima and MSD’s Remicade infliximabs for treating rheumatoid arthritis and
ulcerative colitis (Source – LIS)
OPHTHALMIC DRUGS
Xalatan rivals aid compliance
G
laucoma patients are more likely to adhere to their medication
when switched from a brand to a generic drug, according to a
study of 8,427 patients published online by Ophthalmology, the
journal of the American Academy of Ophthalmology.
Researchers from the University of Michigan examined data taken
from patients taking a prostaglandin analogue (PGA) – such as
latanoprost, bimatoprost or travoprost – 18 months before and after
the first US generic PGA was introduced, Pfizer’s Xalatan
(latanoprost), four years ago (Generics bulletin, 8 April 2011, page 22).
Adherence in patients who switched from Lumigan (bimatoprost)
to generic latanoprost improved on average from 47% of the time to
61% of the time, while for Travatan (travoprost) that figure increased
from 43% to 54%. Researchers speculated that the lower cost of the
generic was the “primary reason” for improved compliance.
“Individuals’ out-of-pocket costs for glaucoma medications can
exceed US$100 per month,” the study noted.
G
27 February 2015
Gen 27-02-15 Pgs.30 Events_Layout 1 25/02/2015 18:35 Page 2
EVENTS
focusing on the improvement of generics
quality and transition from imitation to
innovation. WCGF will provide
communication and exhibition platforms
for chemical drug professionals in China
and abroad and promote international
cooperation and interaction.
MA R CH
4-5 March
■
World Generic Medicines
Congress Europe 2015
Madrid, Spain
Topics covered at this two-day conference
will include growth strategies, pricing,
biosimilars, legal issues and market trends.
Contact: Health Network Communications.
Tel: +44 207 092 1210.
E-mail: customerservices@healthnetwork
communications.com.
Website: www.healthnetworkcommunications.com.
Contact: Violet Chang.
Tel: +86 21 51869310.
E-mail: marketing@bmapglobal.com.
Register online at www.wcgenericsforum.com.
Cascais, Portugal
This meeting provides a forum for businessdevelopment decision makers to discuss and
negotiate agreements, in-licensing, marketing
and distribution of patented medicines,
generics, biosimilars, OTC products,
medical devices and food supplements.
■
Contact: Ray Fu.
Tel: +86 21 51869310.
E-mail: marketing@bmapglobal.com.
Register online at www.wcbiosimilarsforum.com.
World-China Generics Forum
Shanghai, China
“World-China Generics Forum (WCGF)”
calls for high-quality and high-end generics,
M AY
27-28 May 2015
■
Paris, France
Issues to be covered at this three-day event
include innovation, clinical trials legislation
and medical devices. There will be speakers
Contact: Julie Tam, CGPA. Tel: +1 416 223 2333.
E-mail: julie@canadiangenerics.ca Website: www.igpa2015toronto.com.
World Biosimilar
Congress USA
San Diego, USA
Topics looked at during this two-day
conference will include biosimilar
development and regulation, clinical
studies, reimbursement and legal strategies.
DIA 27th Annual
EuroMeeting
Toronto, Canada
This three-day event is being organised by the Canadian Generic
Pharmaceutical Association. It is the annual joint meeting of the Canadian, European,
Japanese, Jordanian, South African and US generics industry associations, the CGPA,
EGA, JAPM, JGA, NAPM and GPhA. Pharmaceutical executives have the opportunity to
take part in conference workshops, and listen to industry experts discuss current issues
regarding the international pharmaceutical sector during a full schedule of plenary
sessions. There are also opportunities to network.
27 February 2015
Contact: Lucia Romagnoli, GPA Conferences.
Tel: +44 7562 876 873.
E-mail: events@egagenerics.com.
Register online at www.egagenerics.com or
www.egaevents.org.
13-15 April
18th IGPA Annual Conference
13th EGA International
Biosimilars Conference
London, UK
This meeting is organised by the EGA
and will cover topics including industry
developments and regulatory issues for
the biosimilars industry.
AP R I L
16-19 September
23-24 April
■
11th EGA Legal
Affairs Forum
Contact: Lucia Romagnoli, GPA Conferences.
Tel: +44 7562 876 873.
E-mail: events@egagenerics.com.
Register online at www.egagenerics.com or
www.egaevents.org.
■
24-26 March
■
Contact: Oxford Global.
Tel: +44 1865 248455.
E-mail: info@oxfordglobal.co.uk.
Website: www.oxfordglobal.co.uk.
Brussels, Belgium
This is a two-day event organised by
the European Generic medicines
Association (EGA) which will look at
issues including litigation, regulatory
matters and patent settlements.
2nd World-China
Biosimilars Forum
3rd Annual Biosimilars &
Biobetters Congress
London, UK
This event will address topics including
market access and strategies. Presentations
will provide information on emerging
markets as well as global commercialisation
strategies. The development of biosimilars
and biobetters will be the focus of day two.
26-27 March
Wuhan, China
“World-China Biosimilars Forum (WCBF)” is
an international conference which is claimed
to be the only event in China to provide a
platform of technical exchange and strategic
collaboration for Chinese biosimilar players
and regulators and global leading biopharmas.
■
■
EU Biosimilar Registration
and Marketing Requirements
Contact: Informa UK.
Tel: +44 20 7017 7481.
E-mail: registration@pti-europe.co.uk.
Website: www.pti-global.co.uk.
18-20 March
■
20-21 April
London, UK
An interactive two-day training course
that will look at practical solutions on
how to gain regulatory approval through
fast, compliant registration applications.
EuroPLX 57
Contact: Raucon.
Tel: +49 6221 426296 0.
E-mail: meetyou@europlx.com.
Website: www.europlx.com.
Contact: DIA.
Tel: +41 61 225 5151.
E-mail: diaeurope@diaeurope.org.
Website: www.diaeurope.org.
23-24 March
■
9-10 March
■
from firms including Amgen and Sanofi.
Contact: Terrapinn.
Tel: +1 212 379 6322.
E-mail: enquiry.us@terrapinn.com.
Website: www.terrapinn.com.
J U NE
8, 9-10 June
■
6th European
GMP Conference
Heidelberg, Germany
This two-day conference will discuss
current and planned changes to the good
manufacturing practice (GMP) regulation.
Contact: Concept Heidelberg.
Tel: + 49 6221 84 44 34.
E-mail: info@concept-heidelberg.de.
Website: www.gmp-conference.org.
Gen 27-02-15 Pg.31 Pricewatch_Layout 1 25/02/2015 18:40 Page 3
PRICE WATCH ............ UK
Escitalopram discounts settle quickly
I
Price (£)
10
Jan 15
Dec 14
Nov 14
Oct 14
Sep 14
Aug 14
Jul 14
Jun 14
May 14
0
Apr 14
5
Figure 1: Average trade, Drug Tariff, Brand and Parallel Import prices for 28-tablet
packs of escitalopram 5mg since generic launch (Source – WaveData)
Escitalopram 20mg
Drug Tariff
Escitalopram 20mg
30 Trade Average
Cipralex 20mg
Trade Average
Cipralex 20mg
Parallel Import
25
Price (£)
20
15
10
Jan 15
Dec 14
Nov 14
Oct 14
Sep 14
Aug 14
Jul 14
Jun 14
May 14
0
Apr 14
5
Figure 2: Average trade, Drug Tariff, Brand and Parallel Import prices for 28-tablet
packs of escitalopram 20mg since generic launch (Source – WaveData)
Escitalopram 5mg
Cipralex 5mg
Cipralex 5mg Parallel Import
80
60
40
Jan 15
Dec 14
Nov 14
Oct 14
Sep 14
Aug 14
Jul 14
Jun 14
0
May 14
20
Apr 14
Number of price offers
100
Figure 3: Price offers for 28-tablet packs of escitalopram 5mg made each month
by generics suppliers to independent pharmacists (Source – WaveData)
100
Escitalopram 20mg
Cipralex 20mg
Cipralex 20mg Parallel Import
80
60
40
Jan 15
Dec 14
Nov 14
Oct 14
Sep 14
0
Aug 14
20
Jul 14
■ For further information see www.bppi.co.uk.
Alternatively, contact Charles Joynson at
WaveData Limited, UK. Tel: +44 (0)1702 425125.
E-mail: cjoynson@wavedata.co.uk.
15
Jun 14
Please specify the product and period of time you would like to
investigate and email your request to info@wavedata.co.uk.
Cipralex 5mg
Parallel Import
20
May 14
Long-term product price trends or other price analyses are available.
Cipralex 5mg
Trade Average
25
Apr 14
WANT MORE LIKE THIS?
Escitalopram 5mg
Drug Tariff
Escitalopram 5mg
30 Trade Average
Number of price offers
n June of last year, we noted that escitalopram had started life as
a commodity generic, and contrasted its dramatic price fall at
launch with that of generic citalopram more than a decade earlier
(Generics bulletin, 20 June 2014, page 25). Citalopram had been
introduced in the UK at the start of 2002 with prices offering a 10%
discount to the Cipramil brand. More than two years later, the average
trade price of citalopram was still more than 50% of the brand price.
Launch prices for citalopram’s successor – effectively on Monday,
2 June 2014 – offered a 90% discount to Lundbeck’s Cipralex brand.
Actavis and Teva both launched immediately upon expiry of the brand’s
supplementary protection certificate on 31 May.
Looking back over the six months that escitalopram has been
on the market, it is clear that little has changed in the generic’s price,
but a lot has happened to pharmacists’ dispensing margins. The
average prices at generic launch offered to independent pharmacists
and dispensing doctors were £0.88 (US$1.36) for the 5mg strength,
£1.18 for 10mg and £2.00 for 20mg. This compared with £8.97, £14.91
and £25.20 for the equivalent Cipralex strengths, or between 90%
and 92% discount to the brand price.
Average trade prices for the two lower strengths were just £0.04
or £0.02 lower last month than they had been the previous June. The
price of the 20mg strength, however, had dropped to £1.76, which
represented a 93% discount to the brand equivalent.
Meanwhile, the Drug Tariff of pharmacy reimbursement prices
had changed in October 2014 from category C – the Cipralex trade
price – to category M, which is based on actual generic trade prices
in the marketplace. The result was as dramatic as the price fall on Day
1 and had the same effect on pharmacists’ dispensing margins. For
four months they had enjoyed margins of 90% or more on average,
but these were suddenly reduced to 44% for the 5mg strength (see
Figure 1) and as low as 33% for 20mg (see Figure 2).
Today, pharmacists’ dispensing margins are even tighter, having
fallen on average to 30% for the highest 20mg strength, 33% for
the 10mg strength and 39% for the 5mg presentation.
In terms of trade marketing activity, escitalopram got off to a
slow start. Despite the large discounts on offer, WaveData only
recorded 10 price offers in the first full month on the market of
escitalopram 5mg from generics manufacturers and wholesalers to
independent pharmacists and dispensing doctors (see Figure 3).
Similarly, there were only 14 for the 20mg strength (see Figure 4).
In subsequent months, however, the activity has been fairly
consistent, peaking in July – the second full month after launch –
with about 70 price offers, and settling to about 60 more recently.
This measure of competitive activity compares with monthly scores
of over 100 price offers for the most active ‘fast movers’, such as
omeprazole, lansoprazole and simvastatin.
Although the average prices of escitalopram changed little over
the six months, some suppliers questioned whether the Day 1 price
discount had been too steep. There were shallow price peaks in July
when the competition started to get heated, with average prices of £1.08
for the 5mg strength, £1.66 for 10mg and £2.82 for 20mg.
G
Figure 4: Price offers for 28-tablet packs of escitalopram 20mg made each
month by generics suppliers to independent pharmacists (Source – WaveData)
27 February 2015
BUSINESS STRATEGY
Pfizer eyes two top spots
with Hospira acquisition
A
Pfizer expects its
US$17 billion deal
to acquire Hospira
will make the
combined company a
market leader in both
generic injectables
and in the burgeoning
biosimilars arena.
David Wallace reports.
mid a climate in which mergers and acquisitions
involving generics firms are not uncommon,
Pfizer’s deal to acquire Hospira still stands out
for its sheer scale. And the originator’s goal with the
US$17 billion deal is similarly broad: to become a
leading global player in the two “large and growing
categories” of generic injectables and biosimilars.
Acquiring Hospira will let Pfizer “vault into a
leadership position in the large and growing off-patent
sterile injectables marketplace”, a global market that
the brand company said would be worth around US$70
billion in 2020. The market’s compound annual growth
rate (CAGR) of 10% over the next five years would
be driven by growth in China and the US, as well as
emerging markets, Pfizer stated.
Meanwhile, the deal would also allow Pfizer to
“advance its goal to be among the world’s most preeminent biosimilars providers”, taking a leading role
in a market that the firm said would grow to be worth
US$20 billion in 2020, as global development, regulatory
and intellectual-property pathways became clearer.
Combining the two companies reinforced the
growth strategy of Pfizer’s Global Established Pharma
(GEP) unit “to build a broad portfolio of biosimilars
in Pfizer’s therapeutic areas of strength through the
addition of Hospira’s portfolio that includes several
marketed biosimilars,” the originator stated.
John Young, who heads Pfizer’s GEP business, said
Pfizer would use its global scale and commercial
network to take the overall portfolio that Hospira
marketed mainly in the US and Europe into emerging
markets in regions such as Asia-Pacific – including
China – and Latin America.
Hospira’s “broadest portfolio in the industry”
would complement the ability to develop niche generic
injectables that Pfizer had gained through last year’s
US$360 million takeover of Innopharma (Generics
bulletin, 8 August 2014, page 3), Young said. He
also highlighted the considerable capacity and lower
costs offered by Hospira’s steriles facility in Vizag,
India, that is awaiting approval from the US Food
and Drug Administration (FDA).
Pfizer anticipates the transaction delivering
US$800 million of annual cost savings by 2018, half
Annual sales
(US$ millions)
Reported
change (%)
Constant-currency
change (%)
2,433
336
266
3,035
+12.5
+0.8
+1.1
+10.0
+13.2
+0.7
+5.8
+11.0
Americas
EMEA
Asia-Pacific
Specialty Injectables
Devices
840
+9.1
+10.8
Other Pharma
589
+24.4
+24.3
4,464
+11.5
+12.5
Hospira
Figure 1: Breakdown by product type and region of Hospira’s sales in 2014 (Source – Hospira)
27 February 2015
of which are to be delivered in the first year after
closing, which is expected in the second half of this
year. More than half the savings are to come from
selling and administrative expenses, with most of the
remainder derived from cost of goods.
Last year, Hospira’s Specialty Injectables
Pharmaceuticals business generated sales that grew by
a tenth to US$3.04 billion (see Figure 1). The Devices
business advanced by almost the same proportion
to US$840 million, while other pharma contributed
US$589 million. Total sales that rose by 11.5% to
US$4.46 billion generated an operating margin that
rose by 10 percentage points to 10.4%.
Price increases and higher volumes in the US
helped to push up overall sales in the Americas region
by 13.5% to US$3.61 billion, or four-fifths of Hospira’s
total (see Figure 2). This rise came despite generic
competition to the firm’s Precedex (dexmedetomidine)
brand and “continued price erosion” for docetaxel.
In Hospira’s Europe, the Middle East and Africa
(EMEA) region, increased volumes for biosimilars –
including Nivestim (filgrastim), Inflectra (infliximab)
and Retacrit (epoetin zeta) – were partly offset by
continued pricing pressure on antibiotics and cancer
drugs, resulting in a reported sales increase for
injectables of just 0.8% to US$336 million. However,
overall turnover in the region was lifted by the Devices
and contract-manufacturing units, rising by 4.6% to
US$532 million.
Meanwhile, in the Asia-Pacific region higher
volumes of Precedex and “strong sales of docetaxel”
in Japan across the region helped to drive a 1.1%
increase in injectables sales to US$266 million. In total,
Asia-Pacific sales rose by 2.6% to US$327 million, or
just over 7% of Hospira’s overall turnover.
In 2014, Pfizer’s sales dropped by 4% to US$49.6
billion as turnover from the originator’s GEP unit slid
by 9% to US$25.1 billion. This was in part due to
increased global competition on Lipitor (atorvastatin)
that cut worldwide brand sales by 11% to US$2.06
billion, as well as generic rivals to Celebrex (celecoxib)
launching in the US late in 2014, which wiped a tenth
off local sales of the brand at US$1.74 billion.
Pfizer’s chairman and chief executive officer, Ian
Read, stressed that Pfizer intended to retain Hospira’s
Devices business – which generates almost a fifth of
the firm’s total sales (see Figure 3) – as part of GEP.
The Hospira transaction would not, Read added,
affect the timing of a decision on whether to split Pfizer
into two businesses – with one covering mature products
and the other innovative and pipeline drugs (Generics
bulletin, 14 November 2014, page 10) – once the
originator had amassed three years of financial data
at the end of 2016.
Outlining Pfizer’s current sterile injectables
capabilities, Read noted that the firm currently had
“a branded portfolio of 73 products across multiple
therapeutic areas, primarily resulting from historic
BUSINESS STRATEGY
acquisitions”. These included anaesthetics, antiinfectives, and oncology drugs.
“The addition of Hospira will greatly expand our
capabilities through the addition of their top-tier and
broad portfolio of organically-grown sterile injectables,
including acute care and oncology injectables,” Read
insisted, highlighting Hospira’s focus on first-to-market
opportunities. He also cited an “untapped demand
for generic sterile injectables in the projected mediumterm in a number of markets”.
Hospira’s current generics pipeline comprises 65
compounds, mostly in the areas of oncology, antiinfectives, anaesthesia and analgesia.
In emerging markets, Read observed, Pfizer’s
“strong brand equity across these geographies” would
allow Pfizer to extend the reach of Hospira’s broad
portfolio into territories “where Pfizer has an extensive
footprint and strong capabilities”.
In particular, suggested GEP president Young, China
– where Pfizer says it has “a much larger and growing
business” compared to Hospira, with a “very large
commercial footprint” – was ripe with “opportunities
for future growth” and synergies.
Meanwhile, Young observed that “the addition
of Hospira comes at a key point in the growth and
development of the biosimilars segment”, with the
firm offering Pfizer “a robust in-line portfolio of
biosimilars and expanded capabilities to capitalise
on growth opportunities”.
Hospira has just rolled out its Inflectra in 24
European countries (see front page), while it also has
exclusive rights to the Celltrion-developed infliximab
in the US and Canada and certain other territories.
A recent US filing for Hospira’s Retacrit biosimilar
rival to two epoetin alfa-based brands – Amgen’s
Epogen and Janssen’s Procrit (Generics bulletin, 6
February 2015, page 19) – has now been accepted by
the US Food and Drug Administration (FDA). The
firm is also developing filgrastim and pegfilgrastim.
And Hospira has also agreed to develop a
trastuzumab candidate through a further collaboration
with Celltrion, and ranibizumab through a deal with
Pfenex (see page 23).
Read described discussions Pfizer would hold with
Hospira’s biosimilars partner, Celltrion, and potential
overlap in biosimilar development programmes as
“not a major issue for the transaction”.
Pfizer is currently enrolling for or conducting
Phase III trials for rivals to Herceptin (trastuzumab),
Rituxan (rituximab) and Remicade (infliximab). It has
just completed a Phase I trial for a version of Avastin
(bevacizumab) and plans later this year to launch a
Phase III trial, while a Phase I trial for Humira
(adalimumab) is underway.
Turning to the subject of Hospira’s past quality
and regulatory issues, Pfizer said it was “comfortable
that the issues raised by the regulators have been
addressed or are being properly addressed”.
At the Vizag injectables plant in India that had
been highlighted by Young as “an important component
for future growth and cost reduction when it comes
on line”, Hospira expects to begin commercial
production “during the first half of 2015”. In early
2014, the plant received 10 ‘Form 483’ observations
from the FDA after a pre-approval inspection, and
the agency is still reviewing additional information
APAC
US$327m, +2.6%
Americas
US$3,605m, +13.5%
EMEA
US$532m, +4.6%
Figure 2: Breakdown by region of Hospira’s sales that increased
by 11.5% to US$4.46 billion in 2014 (Source – Hospira)
Other Pharma
US$589m, +24.4%
Specialty Injectables
US$3,035m, +10.0%
Devices
US$840m, +9.1%
Figure 3: Breakdown by business of Hospira’s sales that increased
by 11.5% to US$4.46 billion in 2014 (Source – Hospira)
supplied by Hospira regarding corrective actions.
Although FDA approval for Vizag was still pending,
Young acknowledged, “immediate approval was not an
essential component of value creation in this transaction”.
Hospira is also currently in the process of
responding to the FDA over deficiencies at its plant in
Irungattukottai, India. Following Form 483 observations
reported at the facility at the end of 2013, the FDA
recently performed a follow-up inspection, resulting
in further observations. The firm has also recently
responded to FDA observations regarding its plant in
Mulgrave, Australia (Generics bulletin, 17 October
2014, page 5).
Having recently announced that it would be closing
its facility in Clayton, North Carolina, in the second
half of 2015 (Generics bulletin, 6 February 2015, page
5), Hospira said this would result in total charges of
around US$45 million, including a US$21.9 million
impairment charge in the Americas segment for 2014.
However, the firm’s Rocky Mount facility – also
in North Carolina – was upgraded by the FDA to
‘voluntary action indicated’ status a year ago, and no
Form 483 observations were issued after the agency’s
latest inspection in June.
Despite these ongoing regulatory and compliance
issues, Pfizer said it was “comfortable with the
transaction” based on a review it had completed of
Hospira’s “key sites”.
“We see the addition of Hospira as providing us
with a durable growth opportunity,” Read concluded,
“driven by their broad portfolios of sterile injectables
and biosimilars, technical manufacturing capabilities,
and our ability to grow the portfolio with our commercial
capabilities, global scale, scientific expertise and worldclass development skills.”
G
27 February 2015
“The addition of
Hospira comes at a key
point in the growth and
development of the
biosimilars segment”
PEOPLE
APPOINTMENTS
Bayer’s Brandicourt
leads Sanofi as CEO
S
anofi has named Olivier Brandicourt – currently chairman of
Bayer HealthCare’s board – as its chief executive officer.
Brandicourt, who joined Bayer in 2013 having previously led
Pfizer’s Emerging Markets and Established Products business units,
will take the reins at Sanofi from 2 April. Until that time, Sanofi’s
chairman, Serge Weinberg, will remain in temporary charge.
Sanofi has lacked a permanent head since late October, when
Chris Viehbacher was ousted after six years at the helm following a
fall-out with the board (Generics bulletin, 3 November 2014, page 1).G
RESIGNATIONS
Frost resigns from Teva board
F
ormer Teva chairman Phillip Frost has given up all responsibility
with the company after resigning from the Israeli firm’s board.
Having announced his intention to retire as chairman midway
through last year after four years in the role (Generics bulletin, 11
July 2014, page 31), Frost was replaced by Yitzhak Peterburg in
December (Generics bulletin, 5 December 2014, page 34). Frost had
joined Teva as vice-chairman in 2006 following the Israeli firm’s
US$7.4 billion acquisition of Ivax.
G
INDUSTRY ASSOCIATIONS
GPhA elects Wheeler as chair
T
he US Generic Pharmaceutical Association has re-elected
Momenta’s president and chief executive officer, Craig Wheeler,
as its chairman. Joining Wheeler on the GPhA’s board are Teva’s
Debra Barrett, Perrigo’s Doug Boothe, Ranbaxy’s Chuck Caprariello
and Fresenius Kabi’s John Ducker, as well as Jeff Glazer from
Heritage, Peter Goldschmidt from Sandoz and Marcy Macdonald
from Impax. Mylan’s Marcie McClintic Coates, Lupin’s Paul
McGarty, Amneal’s Chirag Patel and Par’s Tony Pera also sit on
the board, as do Julie Reed from Hospira, Joseph Renner from
Zydus and Jeff Watson from Apotex.
G
27 February 2015
IN BRIEF
INVENT FARMA, the Icelandic company that in 2005 acquired
Spanish generics and bulk-drugs suppliers Lesvi and Inke
Laboratories, has appointed Ervin Veszprémi as its chief executive
officer. He previously headed Spanish active pharmaceutical
ingredient (API) specialist Medichem.
CUSTOPHARM – the generic injectables drug-services firm based in
Carlsbad, California – has recruited former Bedford Laboratories
general manager Bill Larkins to serve as chief executive officer after
it was bankrolled by US investor Water Street Healthcare Partners.
Larkins led Bedford, the generic injectables business owned by
Boehringer Ingelheim’s US Ben Venue subsidiary – that was recently
bought by Jordanian firm Hikma in a deal worth up to US$300 million
(Generics bulletin, 6 June 2014, page 3) – from April 2012 to
December last year. Larkins has previously worked as a director for
Sandoz, Pfizer affiliate Wyeth and Teva subsidiary Barr.
APMGR – Romania’s generics industry association – has re-elected
Dragos Damian, chief executive officer of Ranbaxy’s Terapia
Ranbaxy Romania subsidiary, as its chairman and president for a
further term. Damian has served as the association’s president since
it was established six years ago. Meanwhile, APMGR has also elected
Krka’s Amelia Tataru and Sandoz’ Cezar Zaharia to its board
of directors. Along with Damian, the pair join a board consisting
of Zentiva’s Simona Cocos and Teva’s Artur Banaszak.
MCKESSON has appointed Bansi Nagji as its head of corporate
strategy and business development. Nagji replaces Brian Tyler – who
has taken up the role of president of McKesson’s North American
Pharmaceutical Distribution and Services unit – and will in his new
role report directly to the US wholesaler’s chairman and chief
executive officer, John Hammergren.
BOEHRINGER INGELHEIM has named Ivan Blanarik as
director of global biosimilar development, based at the group’s
headquarters in Ingelheim. Pavol Dobrotskiy will take current
responsibilities from Blanarik when he becomes Boehringer’s
Russian general director and head of sales and marketing of
prescription medicines from 1 March.
PERRIGO has appointed Jon Michael Pardo as human resources
manager for the firm’s topical drugs facility in Bronx, New York.
He will be responsible for employee and labour relations as well
as “strategic and operational roles” for Perrigo’s New York and
New Jersey sites.
G
PEOPLE
RESHUFFLES
RESIGNATIONS
A
U
Actavis reveals its FDA Commissioner
local generics heads Hamburg steps down
ctavis has unveiled the regional presidents and corresponding
country managers that will lead its generics division once it
completes its US$66 billion merger with Allergan (Generics bulletin,
5 December 2014, page 3).
Of six regional presidents, five will report to president of
International Generics, Lars Ramneborn. The only exception will
be Jean-Guy Goulet, head of generics in Canada and Latin America,
who will report directly to incoming president of Generics and Global
Operations, Robert Stewart, a new role created by Actavis that sees
Stewart replacing David Buchen as head of Actavis’ generics arm.
Only one Allergan employee, Camilla Hartvig, will oversee an
Actavis generics region within the proposed combination. She will
balance her role as head of generics for Actavis’ Nordics region with
those as country manager for Denmark, and oversee a team consisting
of Christian Jonsson in Finland, Thordis Olafsdottir in Iceland,
Fredrik Juserius in Norway and Carl-Johan Lye in Sweden.
Actavis’ Central and Eastern Europe generics business – consisting
of the Baltic States, the Czech Republic, Hungary and Slovenia, Poland
and Slovakia – will be led by Josef Valenta. Respectively, those
country managers will be Giedre Bieliauskaité, Jana Bánhidalová,
Gyorgy Varadi, Izabela Zimmermann and Milan Cernek.
The company’s South Eastern Europe unit, which will fall under
the remit of Peter Bergquist, will consist of Iliya Pashov in Bulgaria,
Makis Economou in Greece, Dan Ivan in Romania and Pavle
Marjanovic in Actavis’ Serbia and Adria segment.
Meanwhile, Grigoriy Chudakov will lead Actavis’ generics
business in Russia, Ukraine and the Commonwealth of Independent
States (CIS) and will supervise Alena Vitorskaya in Belarus, Murat
Nigmatov in Kazakhstan, Volodymyr Mitin in Ukraine and
Moldova and Gairat Gulyamov in the Caucasus and Central Asia
segment. Chudakov will also serve as country manager for Russia.
Finally, Sara Vincent will head Actavis’ UK and Ireland unit,
along with serving as country manager in the UK. Tony Hynds will
oversee Actavis’ operations in Ireland.
S Food and Drug Administration (FDA) commissioner
Margaret Hamburg has announced that she will step down at
the end of March after nearly six years in the role. Following her
resignation, the FDA’s chief scientist, Stephen Ostroff, will pick up
Hamburg’s responsibilities on an acting basis while the agency seeks
a permanent replacement.
Having being appointed commissioner in May 2009 following
nomination by US President Barack Obama (Generics bulletin, 1
June 2009, page 27), Hamburg, 59, has overseen the implementation
of reforms including the introduction of the Generic Drug User Fee
Amendments (GDUFA) in 2012. She has also overseen the progress
of a US biosimilar pathway, which has resulted in Sandoz’ filgrastim
candidate recently receiving a recommendation for approval.
Applauding the “significant progress” the FDA had made under
Hamburg, the US Generic Pharmaceutical Association (GPhA) said she
had been a “tireless advocate for patient safety” and a “leader in efforts
to assure that FDA decisions are guided by scientific principles”.
Meanwhile, Robert Califf, vice-chancellor of clinical and
translational research at Duke University, will join the FDA in “late
February” as Deputy Commissioner for Medicinal Products and
Tobacco. Califf, the FDA noted, would in his new role provide “executive
leadership” to the FDA’s Center for Drug Evaluation and Research
(CDER) and Center for Biologics Evaluation and Research (CBER). G
Follows Boyer and Swanton appointments
These pending appointments come soon after Actavis announced
senior leadership positions within the proposed combination with
Allergan, including the appointments of Andy Boyer as head of US
generics and Wayne Swanton as head of global generics operations
President and chief executive officer Brent Saunders and
executive chairman Paul Bisaro will keep their respective roles
following the close of the transaction.
Meanwhile, Actavis has announced that four directors will resign
from its board as part of the company’s plans to simultaneously
accommodate two Allergan directors as stipulated under the merger
agreement, and reduce the size of its board from 14 to 12 members
as decided in a recent board meeting.
Announcing that Tamar Howson, John King, Jiri Michal and
Andrew Turner would be leaving its board either upon the close of
the transaction or Actavis’ 2015 annual general meeting, the company
insisted the resignations were “not the result of any disagreement with
Actavis on any matter relating to its operations, policies or practices”.
The selection of the Allergan directors was “ongoing”, noted
Actavis, which has not yet allocated a role for the US originator’s chief
executive officer, David Pyott, within the proposed combination. G
27 February 2015
Generics House Ad AUGUST 2014_Layout 1 03/09/2014 10:04 Page 1
Generics bulletin print
Generics bulletin-i digital
News@Genericsbulletin
electronic newsflash
The best decision-makers in the generics industry don’t have the
time to go looking for good information. They let it come to them.
They subscribe to Generics bulletin.
Join thousands of subscribers from competitor companies in
nearly 60 countries who are already benefitting from commercial
intelligence about business opportunities in the global generic
medicines and biosimilars markets.
GOOD VALUE - Individual subscription rates start from just £895
AVAILABLE INSTANTLY WORLDWIDE
Generics bulletin-i is the digital i-edition of Generics bulletin.
Now available online for desktop access, it delivers the
latest Generics bulletin on the day of publication with no postal delay. It also comes – at NO EXTRA
CHARGE – as an app for mobile access by tablet and smartphone.
INDIVIDUAL SUBSCRIPTIONS
An annual subscription comprises:
n 20 Generics bulletin newsletters;
n AND at least 46 weekly
News@Genericsbulletin electronic
newsflashes containing the week’s top
news stories (currently delivered by email).
CHOICE OF FORMATS
The 20 Generics bulletin newsletters
are available:
n EITHER as the digital Generics bulletin-i
for online access by desktop AND tablet
and smartphone. These mobile devices can
have Apple or Android operating systems;
n OR in traditional hard-copy print format,
delivered by airmail;
CORPORATE SUBSCRIPTIONS
A corporate subscription provides location-,
country- or company-wide access to
Generics bulletin-i subscribers also get access to a fully-searchable archive. This contains over
Generics bulletin-i.
five years of generics news and analysis in more than 100 back issues. These offer an invaluable
resource for researching marketing opportunities, benchmarking competitive strengths, evaluating
Contact subscriptions@Generics-bulletin.com.
regulatory changes and assessing product developments.
Existing subscribers can get 20% OFF when they upgrade their subscriptions
to include Generics bulletin-i. Contact subscriptions@Generics-bulletin.com.
Take out a subscription TODAY at www.Generics-bulletin.com or contact: subscriptions@Generics-bulletin.com
Bulletin Publishing Group, OTC Publications Ltd, 4 Poplar Road, Dorridge, Solihull B93 8DB, UK. (Tel: +44 (0)1564 777550; Fax: +44 (0)1564 777524).
Registered in England No: 2765878. VAT No: GB 608 0432 69

major European markets

Transcription

Similar documents

Teva Overview

Sunil Thacker - STA Law Firm

January 2015 - Con

Teva`s Olafsson starts global markets review

Please Join Us at OMTEC Booth 313

Seventy-Five Years of Educational Reform

Issue 6 – 9th October 2015

SlAge:j yrs lsex: lUate

November 2013 - The Palmas Academy