Citeline Pharma R&D Annual Review 2015 Supplement: New Active

Citeline Pharma R&D
Annual Review 2015
Supplement: New Active
Substances Launched
During 2014
Ian Lloyd
Senior Director, Pharmaprojects/Pipeline and Data Integration
Following on from our review of trends in the current pharmaceutical R&D pipeline,
published in early February 2015, this supplement takes a look at the industry’s success
stories of 2014 – the drugs which were launched on to the market for the first time during
the year. Our survey focuses exclusively on new active substances (NASs): new chemical
or biological entities where the active drug had received no prior approval for human use.
As such, this list represents a subset of all the first launches which Citeline reported during
2014, excluding as it does the 51 new drug launches with reformulated or non-NAS
moieties, or biosimilars.
This year, our 2015 Pharma R&D Report showed the pipeline universe to be expanding at
an unprecedented rate and in all dimensions. More drugs are in development than ever
before, at all phases, and in all therapeutic areas. But a cynic might suggest that all this
energy is being wasted unless it leads to the birth of new star products – drugs actually
successfully reaching the market. This supplement thus adds this perspective, and we’ll look
not only at overall numbers, but at drug types, the leading players, and crucially, which of
the new stars in the pharma firmament are shining with novel properties. And in short,
it looks as though 2014 was nothing short of dazzling!
2
Sixty-one NASs – we have lift off!
With no fewer than 61 new active substances reaching the market for this first time in 2014, last year broke
all records. Just how outstanding the last twelve months have been is visible clearly in Figure 1, which
looks at the NAS launches by year since the turn of the millennium. This shows that 2014 soared past the
previous record-holder, 2013, to take the crown as the best year ever, leaving that year’s total of 48 NASs
for dust. As before, we’ve also highlighted how many of the total can be accounted for by vaccines, as
quite often a public health crisis, such as bird ‘flu, can lead to a flurry of launches of novel but ostensibly
similar new vaccine products in response. There were only six vaccines launches in 2014, and these were a
relatively diverse bunch; the next surge will likely be a brace of Ebola vaccines which will hopefully come to
the market in 2015 or 2016.
Figure 1. Number of NAS Launches by Year, 2000–2014, with Numbers Excluding Vaccines Also Shown for 2007–2014
70
Vaccines
Other NASs
60
6
50
40
8
1
30
20
1
38
39
10
0
33
35
31
28
26
31
11
1
3
11
55
35
36
37
37
2011
2012
2013
26
17
2000 2001
2002 2003 2004 2005 2006 2007
2008 2009 2010
2014
Source: Pharmaprojects ®, February 2015, Citeline
So the underlying, vaccine-free picture is even stronger: 55 new molecules in 2014, compared with 35-37
in each of the four previous years. This puts this period light years ahead of any others. But will 2014’s
meteoric rise also turn out to be as transient as a shooting star? Arguably, productivity at this rate must be
sustained if the increases in pipeline size we’ve already seen are going to be supported by new income.
But one could at a stretch apply a line of best fit along the data from 2007 onwards to indicate a sustained
upward trajectory. However, a few late-stage failures this year could easily see things crash to Earth just as
quickly, so it’s best not to get too hyperbolic just yet.
3
The 2014 NAS stats: novelty, breakthroughs,
but mixed-fortunes for big pharma
The full alphabetical list of NASs for 2014 is collected in Table 1. Included in the table are the drugs’
generic and trade names, their mechanisms of action, the companies which have launched them, the
diseases they are launched for, and the country and month of first launch. We have also included an
indication of whether or not they have received orphan drug status in at least one market, and whether or
not they can be considered novel in terms of whether a drug with the same mechanism(s) is already on the
market or not. This last metric, highlighted in the column headed ‘First in Class’ reveals that twelve of
2014’s debutant drugs are novel, indicating a good year for innovation too. There were ten in 2013, so the
proportion is very slightly lower. But if anyone a year ago had offered the industry a year with 61 NASs of
which almost 20% are novel, I’m pretty sure it would have said ‘”Yes, please!”.
Table 1. New Active Substance Launches 2014
Generic
name
4
Trade
name
Company
Indication
Mechanism
of action
Country
of first
launch
Month
of first
launch
First in
Class
Orphan
Drug
Status
USA
July
No
No
albiglutide
Tanzeum
GlaxoSmithKline
Type 2 diabetes
Glucagon-like
peptide 1 agonist
alectinib
hydrochloride
Alecensa
Roche
Non-small cell
lung cancer
ALK receptor
tyrosine kinase
inhibitor
Japan
Sept
No
Yes
allisartan
isoproxil
Xinlitan
Allist
PharmaceutiHypertension
cals /
Shenzhen
Salubris
Angiotensin II 1
antagonist
China
June
No
No
anti-H5N1 avian
influenza
antibodies,
Fab’entech
Fabenflu
Fab’entech
Influenza virus
infection
prophylaxis
Immunostimulant
AsiaPacific
March
No
Yes
apremilast
Otezla
Celgene
Psoriatic
arthritis
Phosphodiesterase
4 inhibitor /
Tumour necrosis
factor alpha
antagonist
USA
April
No
Yes
asunaprevir
Sunvepra
Bristol-Myers Hepatitis-C
Squibb
infection
HCV nonstructural
protein 3 inhibitor
Japan
Sept
No
No
ataluren
Translarna
PTC
Therapeutics
Germany
Dec
Yes
Yes
belinostat
Beleodaq
TopoTarget /
Peripheral T-cell Histone deacetySpectrum
lase inhibitor
Pharmaceuti- lymphoma
cals
USA
Aug
No
Yes
blinatumomab
Blincyto
Amgen
Acute
lymphocytic
leukaemia
CD19 antagonist
USA
Dec
Yes
Yes
conbercept
Compaq
Sipp
Chengdu
Kanghong
Macular
degeneration,
age-related,
wet
Vascular
endothelial growth
factor (VEGF)
receptor
antagonist
China
Feb
No
No
daclatasvir
Daklinza
Bristol-Myers Hepatitis-C
Squibb
infection
HCV nonstructural
protein 5A
Germany
inhibitor
Aug
Yes
No
dalbavancin
Dalvance
Durata
Therapeutics
Cell wall synthesis
inhibitor
July
No
No
Duchenne’s
muscular
dystrophy
Acute bacterial
skin and skin
structure
infections
Ribosomal
readthrough
stimulant
USA
Generic
name
Trade
name
Company
Indication
Mechanism
of action
Country
of first
launch
Month
of first
launch
First in
Class
Orphan
Drug
Status
dasabuvir
Exviera
AbbVie
Hepatitis-C
infection
HCV nonstructual
protein 5B
inhibitor
USA
Dec
No
No
defibrotide
Defitelio
Gentium
Severe hepatic
veno-occlusive
disease
Unidentified
pharmacological
activity
Austria
March
No
Yes
delamanid
Deltyba
Otsuka
Tuberculosis
Cell wall synthesis
inhibitor
UK
May
No
Yes
Duramed
(Teva)
Adenovirus
infection
prophylaxis
Immunostimulant
USA
Oct
No
No
adenovirus Type
4 and Type 7
vaccine, live,
Teva
dulaglutide
Trulicity
Eli Lilly
Type 2 diabetes
Glucagon-like
peptide 1 agonist
USA
Nov
No
No
efinaconazole
Jublia
Kaken
Pharmaceuti- Onychomycosis
cal / Valeant
Cell wall synthesis
inhibitor
USA
July
No
No
efraloctocog
alfa
Eloctate
Biogen Idec
Haemophilia A
Factor VIII
stimulant
USA
July
No
Yes
eftrenonacog
alfa
Alprolix
Biogen Idec
Haemophilia B
Factor IX stimulant
USA
May
No
Yes
eliglustat
Cerdelga
Sanofi
(Genzyme)
Gaucher’s
disease
Ceramide glycosyltransferase
inhibitor
USA
Aug
Yes
Yes
elosulfase alfa
Vimizim
BioMarin
Mucopolysaccharidosis IV
N Acetylgalactosamine 6 sulfatase
stimulant
USA
Feb
No
Yes
empagliflozin
Jardiance
Boehringer
Ingelheim /
Eli Lilly
Type 2 diabetes
Sodium/glucose
cotransporter 2
inhibitor
USA
Aug
No
No
Biotest
Hepatitis-B
infection in
neonates
Immunostimulant
Vietnam
Feb
No
No
Gilead
Sciences
Relapsed
chronic
lymphocytic
leukaemia /
Non-Hodgkin’s
lymphoma
PI3 kinase delta
inhibitor
EU/USA
Oct
Yes
Yes
GlaxoSmithKline /
Kaketsuken
Influenza virus
infection
prophylaxis
Immunostimulant
Japan
March
No
Yes
Influenza virus
infection
prophylaxis
Immunostimulant
India
July
No
No
Type 2 diabetes
Sodium/glucose
cotransporter 2
inhibitor
Japan
April
No
No
Luqa
Gastrointestinal
Pharmaceutidisease
cals
Unidentified
pharmacological
activity
China &
Hong
Kong
June
No
No
hepatitis-B
immunoglobulin
Fovepta
for neonates,
Biotest
idelalisib
Zydelig
influenza
vaccine,
pandemic,
EB66, GSK
influenza
vaccine,
trivalent, LAIV,
Serum Institute
of India
Serum
Nasovac-S Institute of
India
ipragliflozin
Suglat
LQ-006
Astellas /
Kotobuki
luseogliflozin
Lusefi
Taisho /
Novartis
Type 2 diabetes
Sodium/glucose
cotransporter 2
inhibitor
Japan
May
No
No
meningococcal
B vaccine,
Novartis
Bexsero
Novartis
Meningococcal
infection
prophylaxis
Immunostimulant
EU
Jan
No
No
5
Generic
name
6
Trade
name
Company
Indication
Mechanism
of action
Country
of first
launch
Month
of first
launch
First in
Class
Orphan
Drug
Status
meningococcal
B vaccine, Pfizer Trumenba
(suspension)
Pfizer
Meningococcal
infection
prophylaxis
Immunostimulant
USA
Nov
No
No
netupitant +
palonosetron
hydrochloride,
Helsinn*
Helsinn /
Eisai
Radio/
chemotherapyinduced nausea
and vomiting
Neurokinin 1
receptor
antagonist
USA
Oct
No
No
Idiopathic
pulmoary
fibrosis
VEGFR-2 tyrosine
kinase inhibitor /
Platelet-derived
growth factor
receptor kinase
inhibitor / Src
inhibitor /
Lymphocytespecific tyrosine
kinase inhibitor /
LYN tyrosine
kinase inhibitor /
FGF receptor
tyrosine kinase
inhibitor / Vascular
endothelial growth
factor (VEGF)
receptor
antagonist /
VEGFR tyrosine
kinase inhibitor
USA
Oct
No
Yes
PD-1 antagonist /
Anticancer
immunotherapy
Japan
Sept
Yes
Yes
USA
Jan
No
Yes
Akynzeo
nintedanib
Ofev
Boehringer
Ingelheim
nivolumab
Opdivo
Ono /
Bristol-Myers Melanoma
Squibb
obinutuzumab
Gazyva
Roche /
Biogen Idec
Chronic
lymphocytic
leukaemia
CD20 antagonist
olodaterol
Striverdi
Boehringer
Ingelheim
Chronic
obstructive
pulmonary
disease
Long-acting beta 2
adrenoceptor
(LABA) agonist
EU
April
No
No
ombitasvir +
paritaprevir +
ritonavir**
Viekira
pak
AbbVie
Hepatitis-C
infection
HCV non-structural
protein 3 inhibitor
/ HCV non-structural protein 5A
inhibitor
USA
Dec
No
No
oritavancin
Orbactiv
Eli Lilly /
Targanta
Acute bacterial
skin and skin
structure
infections
Cell wall synthesis
inhibitor
USA
Nov
No
No
pembrolizumab
Keytruda
Merck & Co
Melanoma
PD-1 antagonist /
Anticancer
immunotherapy
USA
Oct
No
Yes
rabies vaccine,
Zydus Cadila
Vaxirab N
Zydus Cadila
Rabies infection
prophylaxis
Immunostimulant
India
Jan
No
No
ramucirumab
Cyramza
Eli Lilly
(ImClone) /
Dyax
Stomach and
oesophageal
cancer
Vascular
endothelial growth
factor receptor 2
antagonist
USA
July
Yes
Yes
ripasudil
hydrochloride
hydrate
Glanatec
D. Western
Therapeutics
/ Kowa
Glaucoma
Rho-associated
kinase inhibitor
Japan
Dec
No
No
serelaxin
Reasanz
Novartis
Heart failure
Relaxin agonist
Russia
April
Yes
No
siltuximab
Sylvant
Johnson &
Johnson
Castleman’s
disease
Interleukin 6
antagonist
USA
May
No
Yes
Generic
name
Trade
name
Company
Indication
Mechanism
of action
Country
of first
launch
Month
of first
launch
First in
Class
Orphan
Drug
Status
UK
Oct
No
No
simoctocog alfa
Nuwiq
Octapharma
Haemophilia A
Factor VIII
stimulant
sofosbuvir +
ledipasvir***
Harvoni
Gilead
Sciences
Hepatitis-C
infection
HCV nonstructural
protein 5A inhibitor
/ HCV nonstructual
protein 5B inhibitor
USA
Oct
No
No
sucroferric
oxyhydroxide
Velphoro
Galenica,
Switzerland /
Fresenius
Hyperphosphataemia
Phosphate
antagonist
USA
March
No
No
susoctocog alfa
Obizur
Baxter
Haemophilia A
Factor VIII
stimulant
USA
Nov
No
No
suvorexant
Belsomra
Merck & Co
Insomnia
Orexin receptor
antagonist
Japan
Nov
Yes
No
tasimelteon
Hetlioz
Non-24-hour
Vanda
Pharmaceuti- sleep-wake
disorder
cals
Melatonin 1
receptor agonist /
Melatonin 2
receptor agonist
USA
April
No
Yes
tavaborole
Kerydin
Anacor
PharmaceutiOnychomycosis
cals /
Novartis
Leucyl-tRNA
synthetase
inhibitor
USA
Sept
Yes
No
tedizolid
Sivextro
Dong-A /
Cubist
Acute bacterial
skin and skin
structure
infections
Protein 50S
ribosomal subunit
inhibitor
USA
July
No
No
tofogliflozin
Apleway
Roche /
Sanofi
Type 2 diabetes
Sodium/glucose
cotransporter 2
inhibitor
Japan
May
No
No
turoctocog alfa
NovoEight
Novo
Nordisk
Haemophilia A
Factor VIII
stimulant
Germany
Jan
No
Yes
umeclidinium
bromide +
vilanterol****
Anoro
Ellipta
Theravance /
GlaxoSmithKline
Chronic
obstructive
pulmonary
disease
Long-acting
muscarinic
antagonist
USA
April
No
No
vaniprevir
Vanihep
Merck & Co
Hepatitis-C
infection
HCV nonstructural
protein 3 inhibitor
/ HCV nonstructural 4A inhibitor
Japan
Nov
Yes
No
vedolizumab
Entyvio
Takeda
Crohn’s disease
& ulcerative
colitis
Alpha4beta7
integrin antagonist
/ Integrin
antagonist
USA
June
No
No
vorapaxar
Zontivity
Merck & Co
Thrombosis
Protease-activated
receptor-1
antagonist
USA
July
Yes
No
Major
depressive
disorder
5 Hydroxytryptamine
1A/1B/1D receptor
agonist / 5
Hydroxytryptamine 3/7
receptor
antagonist / 5
Hydroxytryptamine uptake
inhibitor
USA
Jan
No
No
vortioxetine
Brintellix
Lundbeck /
Takeda
Source: Pharmaprojects ®, February 2015
*nepupitant is the NAS in this combination
**ombitasvir + paritaprevir are both NASs in this combination
*** ledipasvir is the NAS in this combination
****umeclidinum bromide is the NAS in this combination
7
Having said that, no one company can truly be said to have had a stellar year. Leading the way in terms
of bringing new NASs to market were Novartis, Merck & Co and Eli Lilly, with just four (compared to
GlaxoSmithKline’s seven in 2013). These companies head our Table 2, which shows how many NASs each
of the Top 10 pharma companies produced, augmented by any other companies which launched two or
more. GSK features high up the list again, although 3 NAS launches from a pipeline of >250 drugs is maybe
not quite the ROI it would wish to see long-term. One other Top 10 company, Roche, produced three NAS
launches, while the two BIs, Boehringer Ingelheim and Biogen-Idec, punched above their weight in also
delivering three apiece.
Table 2. Top company NAS launch performance 2014
Company
Number of NAS launches 2014
Position by pipeline size in Top 25
Novartis
4
2
Merck & Co
4
6
Eli Lilly
4
10
GlaxoSmithKline
3
1
Roche
3
3
Bristol-Myers Squibb
3
11
Boehringer Ingelheim
3
20
Biogen Idec
3
–
Sanofi
2
8
Takeda
2
9
AbbVie
2
16
Gilead
2
–
Johnson & Johnson
1
5
Pfizer
1
7
AstraZeneca
0
4
Source: Pharmaprojects ®, February 2015, Citeline
Languishing at the bottom of this list are three Top 10 companies: Johnson & Johnson, and Pfizer and
its intended prey from 2014, AstraZeneca. The latter was the only of the biggest of big pharma companies
to launch not a single NAS, although while mounting its defence, it has made much of its late-stage
pipeline and the NASs it could deliver in 2015/16. It will certainly need to fire its boosters this year to
maintain escape velocity and pull clear of Pfizer if it is going to survive. Meanwhile, relative upstart Gilead
is twinkling brightly, expanding its HCV franchise and launching a new leukaemia drug to boot.
8
Talking of cancer, it’s also instructive to segment the year’s new drugs by their primary therapeutic focus,
which is what Figure 2 does. This shows that oncology drugs were, as in the previous year, only the third
most successful group in terms of numbers of market entrants. This is despite taking by far the biggest
chunk of the R&D pipeline and budget. This demonstrates that cancer remains a high-risk area, and it’s
interesting to additionally note that seven of the eight new cancer drugs have orphan drug status. High risk
then, but high return.
Figure 2. 2014 NAS launches by Therapeutic Group
2
2
3
3
2
Alimentary/Metabolic Products
13
Anti-infective Products
Anticancer Products
Blood and Clotting Products
Cardiovascular Products
Musculoskeletal Products
Neurological Products
7
Respiratory Products
Sensory Products
8
21
Source: Pharmaprojects ®, February 2015, Citeline
As in 2013, anti-infectives account for by far the largest group of debuting drugs. The difference this year
is the contribution to this figure by vaccines. Only six of the 21 anti-infective launches in 2014 were
vaccines, compared to ten out of fifteen the year before. So there was a burst of new anti-infective
molecules coming to fruition – fuelled in no small part by the explosive revolution in the hepatitis-C
market. There were no fewer than seven new drugs for this disease reaching the market; now all the
industry has to do is work out how to get them to all of the patients who would benefit from them.
Pricing issues are thus far proving restrictive, but as more and better molecules continue to join the first
generation of direct anti-HCV antivirals, the situation is in rapid flux. In fact, with most of the drugs
approved so far being afforded breakthrough therapy status in some form, the market is evolving so
rapidly that the US FDA is now moving to rescind this status from follow-on drugs which were only granted
it a little over a year ago.
Alimentary/Metabolic was second biggest beneficiary of new drug launches, with thirteen. Type 2 diabetes
again led the way here, with its six new molecules coming in the form of four additional SGLT2 inhibitors
and two GLP-1 agonists. Neurological, the second biggest therapeutic area in terms of pipeline activity,
was once again not very successful in producing new drugs, delivering just three. But there were no new
Dermatological or Genitourinary drugs at all.
9
In terms of the countries which hosted market introductions, the USA was as usual far out in front,
with 34/61 (56%) of NAS launches occurring there first. This is a slightly smaller proportion than in 2013,
but a larger number. The big news this year was Japan’s mighty ten debutants, far exceeding the four
seen in the preceding twelve months. This beat the whole of Europe combined. It was interesting
to see that, with additional Asian contributions from China, India and Vietnam, the pharma star was
certainly rising in the East.
Figure 3. 2014 NAS launches by region
3
2
2
3
USA
Japan
China
Other EU
Germany
4
India
UK
3
34
Other
10
Source: Pharmaprojects ®, February 2015, Citeline
The big news this year was Japan’s
mighty ten debutants, far exceeding
the four seen in the preceding
twelve months. This beat the whole
of Europe combined.
10
The novel NASs of 2014 – some stellar advances,
but some astronomical prices
We now move on to highlighting the most exciting new drugs of 2014 – the twelve novel NASs. These are
the drugs hitting the market with a mechanism of action which has not been seen in a launched drug
before. They break down this year into three anti-infectives, four anticancers, and one apiece for blood/
clotting, cardiovascular, metabolic, musculoskeletal and neurological. Four of these drugs also have the
double-whammy of orphan drug status.
Let’s start with what seems very much to be the mal du jour in terms of pharma innovation, hepatitis-C.
Even in almost thirty years of commenting on pharmaceutical R&D, it is still comparatively rare for me to be
able to say in all honesty that the treatment of a disease is undergoing a total revolution. We are not there
yet, but replacing an only partially effective and lengthy treatment regimen including an injectable drug
with potentially severe side-effects, with an all oral, well tolerated 4-6 week treatment with cure rates
approaching 100%, now seems an achievable goal. As previously noted, seven drugs joined the HCV small
molecule armoury last year, and of these two were first-in-class. Bristol-Myers Squibb’s Daklinza
(daclatasvir) was one of these, becoming the first HCV nonstructural 5A inhibitor on the market when it was
first commercialized, in Germany back in August. It is also under Phase II development as part of BMS’s
triple fixed-dose combo, whose other constituents are asunaprevir and beclabuvir. It was joined in October
by the Japanese launch of (Vanihep) vaniprevir. This molecule has dual activity in inhibiting both the NS3
protease and the nonstructural 4A protein, and it is the latter activity which is the novel mechanism here.
This brings the total number of HCV targets hit by direct-acting antiviral small molecules to four. Vanihep is
interesting for its preferential activity on genotype 1 only, which is found in two-thirds of Japanese HCV
patients; Merck has thus decided to only market the drug in this territory.
The third new anti-infective NAS is Kerydin (tavaborole), the first leucyl-tRNA synthetase inhibitor to make
it through the development process. It’s an antifungal, indicated in the US for the treatment of the nail
infection, onychomycosis. It was developed by Anacor and licensed out to Novartis’ subsidiary, Sandoz.
So in infectious disease, viral and fungal diseases benefitted from novelty, but there was no such good
news for bacterial infections.
The four cancer drugs boasting a novel mechanisms are all also orphan drugs. Ono’s Opdivo (nivolumab)
became the first PD-1 antagonist on the market when it was launched in Japan in September. Ono
partnered with cancer specialist Bristol-Myers Squibb to bring Opdivo through development, picking up
orphan drug status for melanoma in both Japan and the US along the way. Its successful launch meant that
it just pipped Merck & Co’s similar molecule Keytruda (pembrolizumab) to the title of first PD-1 antagonist
available. The PD-1 (programmed cell death 1) protein is a cell surface protein which is here being targeted
by both of these drugs to treat melanoma. As such, these two drugs are among the first market entrants
from the super-hot field of anticancer immunotherapeutics. These particular antibodies have broad
potential use in other cancers too, and indeed Opdivo has already been filed in the EU and US additionally
for non-small cell lung cancer. It was something of the star molecule at November’s AACR-NCI-EORTC
Symposium on Molecular Targets and Cancer Therapeutics meeting, held in Barcelona.
11
It is joined in both its novelty and orphan drug status (ODS) by Blincyto (blinatumomab), the first CD19
antagonist to gain approval, having been brought to market by Amgen for the treatment of adults with
Philadelphia-negative relapsed/refractory B-precursor acute lymphoblastic leukaemia (ALL). First launch
was in the US, where it has ODS and breakthrough therapy status, and it also has ODS in the EU, where it is
awaiting approval. CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes and decreases the threshold for antigen receptor-dependent stimulation. The drug is one of three
monoclonal antibodies in this set of novel anticancers and seven in the NAS list as a whole in what was a
pretty successful year for this class of agents.
The third anticancer MAb with a novel mechanism is Lilly and Dyax’s Cyramza (ramucirumab), which acts via
the new mechanism of direct antagonism of the VEGFR-2 receptor. The drug has been launched in the US
for advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma with
disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Zydelig (idelalisib) is the final anticancer, but in this case is not a MAb. It is a small molecule PI3 kinase delta
inhibitor, and is in fact the first PI3K (phosphatidylinositol 3-kinase) inhibitor of any type to reach the
market. Its US approval for relapsed chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma was
swiftly followed by the nod from the EU, and it is another success story for high-flying Gilead.
There were two other novel NASs which also had the distinction of being orphan drugs. In the metabolic
area, we saw a new molecule for an enzyme efficiency disorder: BioMarin’s Vimizin (eloslfase alfa) for
mucopolysaccharidosis IV. This enzyme replacement therapy has distinguished itself by being another new
drug to command a very high price – an eye-watering £190,000 per year. But with there only being around
3,000 MPS IV patients in total in the developed world, this is the very definition of a rare disease, and with
Vimizin being the only therapeutic drug option, the cost is at least understandable.
The final orphan is Translarna (ataluren) from PTC Therapeutics, which was launched first in Germany for
the treatment of patients with nonsense mutation Duchenne muscular dystrophy. Mechanism-wise, this is
an interesting one. The drug was presumed to act by promoting read-through nonsense mutations in
mRNA; however, it has been suggested that the ascription of this mechanism was due a misinterpretation
of a preclinical result. Nevertheless, it appears to increase dystrophin levels, and received conditional
approval in the EU. It remains in Phase III for another genetic disorder involving nonsense mutations, cystic
fibrosis. For now at least, it is recorded as the first ribosomal read-through stimulant to reach the market.
CNS is an area seemingly hitting something of an impasse at the moment. Despite being the second
biggest therapy area in terms of pipeline, it is showing the lowest growth rate, and has struggled in recent
years to deliver many new compounds. However, one of its three NASs this year did at least exhibit some
novelty. Merck & Co had success in Japan again, here with Belsomra (surovexant), a new insomnia drug
and the first orexin receptor antagonist. It has since also been launched in the US.
12
Finally, there were two first-in-class NASs in the clotting/cardiovascular area. Zontivity (vorapaxar) is
another new drug from Merck & Co. It is the first protease-activated receptor-1 antagonist; other drugs
with this activity, such as Eisai’s atopaxar, fell along the wayside to leave Merck as the sole inhabitant of this
space. It received the green light in the US for use as an antithrombotic in patients with a history of heart
attack or with peripheral arterial disease and no history of transient ischaemic attack or stroke. Lastly, we
have Reasanz (serelaxin) from Novartis for heart failure; the first relaxin. It has been launched in Russia, but
regulatory authorities rejected its first applications in both the EU and the US. Resubmissions are planned
following receipt of results from trials which are currently running, but it would be fair to say that the jury is
still out on this one.
This constellation of first-in-class drugs illuminates Merck & Co as the most successful at delivering novelty
through 2014, with three drugs. This just eclipses Bristol-Myers Squibb, which had two.
This constellation of first-in-class
drugs illuminates Merck & Co as the
most successful at delivering novelty
through 2014, with three drugs.
This just eclipses Bristol-Myers
Squibb, which had two.
13
Orphan drugs put on spectacular display
As well as novel drugs and breakthrough therapies, there was more evidence in 2014 of the industry’s
current fascination with orphan drugs and the high prices which such niche products can command.
Leaving aside the aforementioned pricing issues with the new generation of hepatitis-C drugs (which,
let’s not forget, is nothing like an orphan disease in terms of prevalence), the year saw a historically high
and potentially budget-busting total of 22 NASs launched which have orphan drug status granted in at
least one market. The previous year, there were only twelve, and thus the proportion of NASs which are
orphan drugs has risen from a quarter to over a third.
But for the singular feature which really sets 2014 up as historic, we have to go back to that very first graph
in this report. The pharma R&D universe has been steadily and continuously expanding for many years,
but until now, growth in the number of drugs reaching the market has eluded us. Last year though, this
finally seems to have arrived. The supernova-like explosion of 61 new active substances onto the market
in a single year is completely without precedent, and both exceedingly welcome, and probably a little
surprising too. The birth of a new epoch, or a flash in the pan? After all, supernovae are notorious for
burning brightly and briefly before collapsing, often into black holes. I don’t think that will happen, but
the danger is always that if such a spectacular result is not repeated in 2015, the industry’s mood might
at least darken. For now, let’s just bask in the glow of record-breaking results. Pharmaprojects will be
continually observing the pharma universe as always, watching for more signs and portents.
The supernova-like explosion
of 61 new active substances
onto the market in a single year
is completely without precedent,
and both exceedingly welcome,
and probably a little surprising too.
The birth of a new epoch, or
a flash in the pan?
14
15
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