- Biosimilars

Transcription

- Biosimilars

2016
TRENDS IN
BIOSIMILARS
REPORT
OUR NEXT CHAPTER IN HEALTHCARE
TABLE OF CONTENTS
INTRODUCTION………………………………….………….01
What are Biologics and Biosimilars?, Biosimilars are not Generics, Message from Amgen,
Message from Editorial Council
BIOSIMILARS LANDSCAPE………………………..….05
U.S. Biosimilar Timeline, International Experience UNCOVERING THE UNKNOWNS…………….……..13
U.S. Approval Pathway, Interchangeability & Substitution, Naming, Coding & Payment Guidance
GAME CHANGERS………………………………………....20
Coverage Policies, Provider & Patient Education, Logistics, Manufacturer Reliability & Contracting,
Reimbursement, Safety & Pharmacovigilance
LOOKING AHEAD……………………………………….....47
GLOSSARY………………………………………………….....50
REFERENCES……………………………………………......54
INTRODUCTION
1
INTRODUCTION
WHAT ARE BIOLOGICS AND BIOSIMILARS?
BIOSIMILARS ARE NOT GENERICS
Biologics are therapeutic proteins, such as monoclonal antibodies
(mAbs), that are manufactured from natural sources, including
living “host” systems, such as human and animal cells, yeast, and
bacteria.1 These living systems are genetically engineered to
generate proteins, typically by inserting the genetic sequence,
encoding a therapeutic protein, into the DNA of the host.2 Because
they are small microscopic organisms, the hosts are typically
further engineered to increase the amount of protein they
produce, ensuring that therapeutically useful quantities of protein
can be cultivated.2
Biosimilars are reverse-engineered approximations of marketed
biologics, meaning that biosimilars are highly similar to their
reference products.2 However, due to the incredible complexity
of proteins and the fact that they are literally grown in living
cells, biosimilars are also unique and can never be identical
to the reference product.2 This is in contrast to traditional small
molecule medicines that can be directly copied as generic
compounds in a laboratory.2 Therefore, it can be clearly
stated that biosimilars are not generics and should be
considered differently.
“Biosimilar” is a U.S. Food and Drug Administration (FDA)
designation used to describe a biological product that is
“highly similar” to an approved biologic (known as a reference
product) already being used to treat patients.1 To be classified
as a biosimilar, the protein must have no clinically meaningful
differences in terms of safety and effectiveness from the
reference product; only minor differences in clinically inactive
components are allowed.3
For regulatory and clinical purposes, the inevitable differences
between a biosimilar and the reference product will vary based
on a number of factors, including the manufacturing process
itself, as well as the ability of a biosimilar manufacturer to reverse
engineer, and scientifically document, a highly similar biologic
to the reference product.4 As a result, no two biosimilars are
identical to each other or to the reference product, although
they share many attributes.5
Because biologics and their reference products are never identical,
the Biologics Price Competition and Innovation Act was passed in
2010 to create a separate approval pathway for biosimilars.3,7 Unlike
the abbreviated pathway for small molecules,8 the FDA requires an
additional level of evidence for biosimilars than for generics.9 To be
considered a biosimilar, it must be shown that any subtle structural
or functional differences between the candidate protein and the
reference product do not impact the clinical profile.9 Given all
these differences between biosimilars and generics, it is no wonder
that payers, prescribers, and other decision makers have additional
considerations when evaluating a biosimilar.
2
INTRODUCTION
BIOSIMILARS
LANDSCAPE
MESSAGE FROM AMGEN
Dear Colleagues,
We look forward to working together with you, and we hope the
2016 Trends in Biosimilars Report is a valuable resource for you
and your colleagues as you manage the ongoing introduction,
adoption, and management of biosimilars.
GAME CHANGERS
At Amgen, we know that there are still unknowns in the market
and there is much to learn from one other as we take this next
step in biologic medicine together.
We have taken that approach for this year’s report. Working
alongside an expert Editorial Council comprised of leading
medical and pharmacy directors, as well as employers
representing a broad mix of the U.S. reimbursement community,
we are proud to share the third edition of the Trends in Biosimilars
Report. This report is intended to give stakeholders a guide
to the latest topics, trends, and issues pertinent to biosimilar
introduction and adoption in the U.S.
UNCOVERING THE
UNKNOWNS
This year promises to bring greater clarity to the biosimilar
landscape. In 2015, we witnessed some significant biosimilar
milestones, including the finalization of some of the longstanding draft biosimilar guidances from the U.S. Food and
Drug Administration, as well as the approval and launch of the
first biosimilar in the U.S. With the evolution of this marketplace,
education and informed choice are important components of
biosimilar adoption and utilization. Payers, employers, patients,
pharmacists, physicians, and other key stakeholders all play a
key role as the biosimilars market develops. As a pioneer in the
development and commercialization of biologics medicines,
Amgen has the opportunity to support this education.
DUANE H. BARNES
Vice President & General Manager
U.S. Value and Access, Amgen
LOOKING AHEAD
3
INTRODUCTION
DEAR COLLEAGUES,
The first commercial launch of a biosimilar in the U.S. represented a significant
new development in the biologic market, and it is expected that biosimilars will
play an increasingly prominent role in our value-based healthcare system. To more
fully leverage this trend, we believe that all stakeholders, including payers and
healthcare providers, will benefit from a better understanding of regulatory, policy,
and manufacturing considerations for biosimilar introduction and adoption. Payers
and healthcare providers alike will likely be making specific evaluations and critical
decisions around new biosimilar entrants, in order to determine whether biosimilars
are aligned with a value-based healthcare model’s focus on managing costs, driving
quality care, and achieving intended patient outcomes. The community of health
plans, hospital systems, Integrated Delivery Networks (IDNs), pharmacy benefit
managers (PBMs), employers, and government officials, who determine reimbursement
is already working to evaluate biosimilar therapies, their benefits and their emerging
role in formulary structures and medical coverage policies. Providers and other
stakeholders are also assessing the financial and organizational implications of
biosimilars adoption and acceptance within their institutions, including the educational
and new structural costs (i.e., electronic medical record programming) associated
with biosimilar implementation.
We are proud to contribute to the 2016 Trends in Biosimilars Report, which provides
timely and useful information on some of the crucial biosimilar issues that the broader
healthcare community is grappling with today. It is our hope that this report will serve
as a unique resource for all of those seeking a more complete understanding of these
issues, and to this end we have also included varying stakeholder perspectives to
encourage informed dialogue within the healthcare community. The following pages
first provide an overview of biologics and biosimilars, and then delve more deeply into
a market overview of biosimilars (including an international perspective), pathways
for approval, payment guidance, and potential drivers of success for biosimilars in the
current market.
4
MESSAGE FROM THE
EDITORIAL COUNCIL
This report offers insights from our
Editorial Council, comprised of highly
experienced medical and pharmacy
directors representing the broad
mix of managed care organizations
throughout the U.S., as well as employer
and benefit design consultants.
ROBERT ADAMSON, PharmD
Chief Pharmacy Officer, Barnabas Health
MICHAEL BOSKELLO
Clinical Strategy, Viking Healthcare Solutions
CHERYL LARSON
Vice President, Midwest Business Group on Health
SANDRA MORRIS, RN, MSN, CHC
Former U.S. Benefits Design Senior Manager,
Procter & Gamble Company
PETER NEUMANN, ScD
Director, Evaluation of Value and Risk in Health,
Tufts Medical Center
ELAN RUBINSTEIN, PharmD, MPH
Principal Consultant, EB Rubinstein Associates
KENNETH L. SCHAECHER, MD
Medical Director, SelectHealth
Editorial Council members are participating
independently and their views may not reflect the
interests of their respective companies.
BIOSIMILARS LANDSCAPE
5
U.S. TIMELINE
December 2009
Implementation of the Biologics Price
Competition and Innovation Act3
2008
No guidelines on biosimilars
in the U.S.3
6
2009
2010
March 2010
Pathway passes as part of
the Affordable Care Act3
2011
February 2012
FDA issues draft guidance to assist industry
with development of biosimilars10
20
INTRODUCTION
BIOSIMILARS
LANDSCAPE
CMS issues guidance documents on the
treatment of biosimilar products under
Medicare Part B, Medicare Part D, and
Medicaid Drug Rebate Program15,16,17
April 2015
FDA issues three final biosimilars
guidance documents18
July 2014
FDA accepts application for
first biosimilar in the U.S.11
2013
2014
UNCOVERING THE
UNKNOWNS
012
March 2015
FDA approves the first biosimilar in the U.S.14
July 2015
CMS issues proposed payment provisions
for biosimilars under Medicare Part B19
2015
August 2015
FDA issues draft guidance on biosimilar naming20
GAME CHANGERS
December 2014
3 active FDA filings for biosimilars pending
review as of December 31, 201411,12,13
September 2015
Launch of first biosimilar in the U.S.21
October 2015
CMS finalizes provisions for biosimilars22
November 2015
FDA issues final guidance on formal meetings
between FDA and biosimilar product applicants18
LOOKING AHEAD
December 2015
6 active FDA filings for biosimilars pending review
as of December 31, 201524-29
7
INTERNATIONAL EXPERIENCE
EUROPEAN UNION
Biosimilars, also referred to as follow-on biologics, have limited
exposure to date in the U.S. compared with the rest of the world,
given that the first U.S. biosimilar was approved in March 2015
and launched in September that year.14, 21 Ten years earlier, the
European Medicines Agency (EMA) was the frontrunner in
biosimilar regulation after providing an overarching regulatory
approval framework for biosimilars30 and subsequently
approving its first biosimilar the following year in 2006.31 Since
then, the European Union (EU) has led the world in biosimilar
development, having approved 22 different biosimilar products
as of March 2016.31 In addition to the U.S. and EU, other countries
with leading global pharmaceutical markets, such as, Japan,
Australia and Canada have followed suit, even adapting the
framework provided by the EMA for their respective markets:
11 biosimilars have been approved in Australia since 2010,32
8 biosimilars have been approved in Japan33 and 3 in Canada
since 2009.34 Moreover, as many of the leading biologic products
face patent expiration in mature markets around the world, it is
estimated that the global biosimilar market may reach as high
as $20 billion by 2020.35
The increased availability of biosimilars following the expiry
of patents or other forms of market exclusivity has helped to
advance the progress of biosimilar uptake across EU countries,
although considerable variances in uptake by geography
and therapeutic area persist.37 In 2013, the range of market
penetration for biosimilar human growth hormone (HGH)
products ranged from a low of 2 percent in Norway to a high of 99
percent in Poland.37 Erythropoietin (EPO) biosimilar penetration
has varied in a slightly narrower range, from 1 percent in Croatia
to 62 percent in Bulgaria. Granulocyte-colony stimulating factor
(G-CSF) biosimilar penetration is lowest in Belgium, with 2
percent market share, and highest in Croatia, Czech Republic,
Hungary and Romania, capturing nearly 100 percent share of
the accessible market in these countries.37 This speaks to the
heterogeneity of the EU market and further explains why the
EU experience may not necessarily offer comparable insights on
the trajectory of the U.S. market.
Despite this upward trend in approval of biosimilars, uptake of
these agents has varied across national markets.36 Given the
variability of healthcare system market structures outside the
U.S., translating these experiences to the U.S. may present its
own set of challenges. Nonetheless, key observations from these
markets may provide some insights on how the U.S. biosimilars
market will evolve.
8
In the EU countries with the largest economies, often
referred to as the EU5, uptake has increased over time,
although it remains measured and shows significant
variations (see Figure 1). 37, 38
Hospital or Plan Purchasing: This approach is typically used
when national purchasing does not occur and relies on the
ability of hospitals or plans to negotiate with competing
manufacturers of biologics. Discounts from list price can be
achieved, particularly when negotiating is done at a regional
level.37 In addition, hospitals, pharmacies, and insurance plans
have the discretion to implement their own tender models,
which can have a significant impact on biosimilar adoption.39
Countries using this approach include Italy, Spain, Germany,
and the U.K.37
•
(% OF TREATMENT DAYS, 2013)37
BIOSIMILAR CATEGORY
HUMAN GROWTH HORMONE (HGH)
ERYTHROPOIETIN (EPO)
GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF)
73%
73%
53%
53%
51%
35%
28%
12%
20%
19%
16%
9%
8%
20%
LOOKING AHEAD
Competition-Driven Free Market: This model involves little
to no direct involvement by the payer when setting or
negotiating prices. Instead, manufacturers are free to set
their own price in the setting of free-market competition.
Countries adopting this approach include Belgium, Finland,
and Switzerland.37
FIGURE 1: BIOSIMILAR PENETRATION OF ACCESSIBLE MARKETS
GAME CHANGERS
•
UNCOVERING THE
UNKNOWNS
Tender Model: This model is based on the principle that the
government as the payer will negotiate with the supplier for
the lowest price of a drug. Countries using the tender model
include Poland, Norway, and, to some degree, Hungary, which
helps to explain the significant penetration biosimilars have
achieved in each of these markets.37 The influence of this
approach has been brought into acute focus following the
introduction of the first monoclonal antibody (mAb) in the
EU. Between December 2014 and February 2015, monthly
uptake of the mAb biosimilar has been 46 percent in Poland,
36 percent in Norway, and 19 percent in Croatia, compared
with Ireland that only has 3 percent monthly uptake of the
mAb biosimilar.36
Prescribing, Substitution, and Switching Guidelines and
Mandates: This approach can be used as a stand-alone
policy or in combination with the three models described
previously. In this model, a biosimilar may be mandated as
the first choice in therapy, or prescribing guidelines may
recommend its use as the preferred first-choice treatment.
As of October 2014, Denmark has most extensively used this
approach to influence biosimilar prescribing.37 Across the
EU, decisions on prescribing policies such as substitution
are made at the national level.40 In many countries (e.g., Italy,
Germany), biosimilars are specifically excluded from lists of
products suitable for substitution, whereas in other countries
where substitution is permitted only for International
Nonpropritary Name (INN) only prescriptions, physicians
routinely prescribe biologics by brand.40 In 2013, France
passed a law permitting a restricted form of substitution
wherein pharmacists may dispense a biosimilar product for
a patient who is initiating therapy and has been prescribed
the reference product.41
INTERNATIONAL
EXPERIENCE
•
•
INTRODUCTION
As is the case in most global markets, one of the most
influential factors for biosimilar market penetration is the payer
environment. Four distinct payer models have emerged across
Europe to influence the price and uptake of reference products
and biosimilars:
5%
*Source: Adapted from IMS. Assessing Biosimilar Uptake and Competition in European Markets. 2014.37
9
AUSTRALIA
CANADA
Australia has modeled its approach to biosimilars largely from
the experience in the EU,32 including policies and guidelines to
facilitate the adoption of biosimilars.42 The Australian health
authority recently signed legislation that gives the payer body
exclusive authority to determine substitution of biosimilars at
the pharmacy level.43
Canada independently developed a regulatory framework in
2010 that, similar to the EMA framework, requires head-tohead analytical and clinical comparisons of the biosimilar and
its reference product.30 Biosimilars are still in early development
in Canada, and providers have been slow to adopt biosimilars,
perhaps because of a relative unfamiliarity with the products
compared with providers in more established markets.47 However,
the Canadian healthcare market is undergoing significant change,
with several trends that may affect the future of the country’s
biosimilar market.47 Concurrent with the first introduction of
biosimilars in Canada in 2009, a number of factors that may
influence adoption of biosimilars include: 47
The Australian government has publicly pledged to
invest $20 million Australian dollars in launching a
national education campaign to foster biosimilar
adoption and uptake. 43
In August 2015, Australia’s Therapeutic Goods Administration
(TGA) approved the country’s first biosimilar mAb, infliximab.32
The following December, this biosimilar mAb was officially
added to the Pharmaceutical Benefits Scheme (PBS) with the
recommendation that the biosimilar be substituted for the
reference product at the pharmacy level.45 This means that
pharmacists may offer patients the option of receiving the
reference product or the lower, cost-saving biosimilar. There is
no automatic or uncontrolled substitution of PBS medicines in
clinical practice in Australia, but a pharmacist can substitute a
medicine if: 46
10
•
The prescriber has not ticked the ‘brand substitution not
permitted’ box; and
•
The pharmacist consults the patient before any substitution
occurs; and
•
The patient agrees to the substitution.
•
Transition to a pan-Canadian process for reimbursement
price negotiations;
•
Generally decreased access to physicians, accompanied by
the increasing importance of healthcare provider groups;
•
Movement toward greater reliance on health
economic evidence;
•
Reevaluation of generics pricing regulations; and
•
Resistance to high-cost biologics and drugs for rare diseases.
Within this landscape, provincial payers are emerging as critical
decision-makers in biosimilar uptake, and are evaluating new
therapies based on their clinical and economic value.47 Importantly,
however, since biosimilars are not considered to be therapeutically
or pharmaceutically equivalent to the reference biologic drug,
Health Canada does not support substitution of biosimilars.47,48
INTRODUCTION
JAPAN
February 2016.33 Figure 2 shows how biosimilar use in Japan
compares with that in the EU for erythropoiesis-stimulating agents
(ESAs) and granulocyte-colony stimulating factors (G-CSFs).
Japan, along with the U.S. and EU, holds a large portion of the
healthcare cost burden as it comprises the majority of value size
and growth of the global biologic markets.50
INTERNATIONAL
EXPERIENCE
Japan has a clearly established approval pathway for biosimilars
that is based on EU processes and was published in 2009 by
its regulatory approval agency (Pharmaceuticals and Medical
Devices Agency) and its regulatory body (Ministry for Health,
Labour and Welfare).30, 33 Japan’s first biosimilar was approved
in 2009 and seven subsequent biosimilars were approved as of
PERCENTAGE OF TREATMENT DAYS EXAMPLE
FIGURE 2. COMPARISON OF INNOVATOR (REFERENCE PRODUCTS) AND BIOSIMILAR USE IN THE EU27* AND JAPAN51
ESAs
3%
6%
9%
15%
EU27*
2008
G-CSFs
1%
0%
2008
G-CSFs 0%
2012
2013
2014
36%
50%
60%
67%
2009
2010
2011
2012
2013
2014
0%
7%
36%
57%
69%
75%
2009
2010
2011
2012
2013
2014
0%
0%
0%
0%
3%
15%
2009
2010
2011
2012
2013
2014
Source. Data on File, Amgen. IMS Health MIDAS 2014.
INNOVATOR
BIOSIMILARS
LOOKING AHEAD
2008
2011
GAME CHANGERS
ESAs
JAPAN
2010
29%
8%
21%
2008
% TREATMENT DAYS
2009
25%
UNCOVERING THE
UNKNOWNS
% TREATMENT DAYS
19%
*DOES NOT INCLUDE LUXEMBOURG
11
CANADA
• Government doesn’t provide direction
regarding therapeutic equivalence with
originator products48
• Health Canada does not support
biosimilar substitution47
EUROPE
• Uptake varies over time, between countries and across therapeutic areas36
• Four distinct payer models have emerged across Europe to influence the
price and uptake of reference product and biosimilars37
• Pharmacy-level substitution for biologic drugs is not widely practiced in
any EU country40
JAPAN
• Holds a large portion
of the healthcare cost
burden as it comprises
the majority of value size
and growth of the global
biologic markets50
U.S.
• The U.S. is the only country
that has established a
legislative standard and
definition in order for
an interchangeability
designation to be granted52
12
AUSTRALIA
• New legislation gives the payer body exclusive
authority to determine substitution of
biosimilars at the pharmacy level43
• Substitution of biosimilars recommended as its
default policy43
UNCOVERING THE UNKNOWNS
13
U.S. FDA APPROVAL PATHWAY
In recognition of the unique and complex biological properties
of biologics, the FDA has established a distinct pathway for
the approval of biosimilars.7 This process differs significantly
from that used for approval of small-molecule generics and
carries a higher threshold of clinical evidence.8,9 To receive FDA
approval, generics must be shown to be bioequivalent and have
the same active ingredient, strength, dosage form, route of
administration, and condition of use as the original product.53
Conversely, biosimilars require head-to-head analytical, and
nonclinical and clinical comparisons with a reference product.9
Within this framework, the clinical evidence must be sufficient to
demonstrate that the biosimilar product is highly similar to the
reference product and safe, pure, and potent for one or more
approved conditions of use.9 While the FDA’s approval pathway
is aligned with U.S. law, and therefore it is independent from the
EU framework, both frameworks share a requirement for headto-head analytical, nonclinical, and clinical testing.9, 54
It is important to note that, while a biosimilar may require
fewer clinical trials than its reference product in order to
attain approval, it may also require a greater preponderance
of analytical characterization, and nonclinical and clinical
pharmacology data (see Figure 3).9, 55 Importantly, the FDA does
not require comparative analytical or clinical studies between
two biosimilars.9 This means that biosimilar candidates will be
evaluated only against their reference products and not against
other biosimilars.5
FIGURE 3. CLINICAL DEVELOPMENT OF REFERENCE PRODUCTS AND BIOSIMILARS 9,55
REFERENCE PRODUCT DEVELOPMENT
351(A) Biologics License Application
BIOSIMILAR DEVELOPMENT
351(K) Biologics License Application
SAFETY &
EFFICACY
SAFETY &
EFFICACY
Demonstrate safety,
purity, and potency
CLINICAL PHARM.
(pharmacokinetics/pharmacodynamics)
Demonstrate biosimilarity
to the reference product
CLINICAL PHARM.
(pharmacokinetics/pharmacodynamics)
NONCLINICAL
NONCLINICAL
ANALYTICAL CHARACTERIZATION
(structure & function assessment)
ANALYTICAL CHARACTERIZATION
(structure & function assessment)
Source. Graphic was adapted from Kozlowski S. Presented at: Biotechnology Technology Summit; June 13, 2014; Rockville, MD.
14
Clinical Studies
One study to inform
immunogenicity and will likely
need at least one clinical study
in a sensitive population to
confirm safety and efficacy
When the FDA approves a sponsored product as a biosimilar, it is
not automatically considered interchangeable with its reference
product, and it should be noted that only the FDA can grant
this designation of interchangeability, which requires additional
RUNNERS
SLIDEthat
/ IMAGE
evidence
beyond
required for FDA approval.3 To be deemed
interchangeable, the product must be approved as a biosimilar,
and the sponsor must provide evidence of an expectation of
the same clinical result as the reference product in any given
patient.7 For a product that is administered more than once,
the sponsor must also prove that there are no additional risks
to safety or diminished efficacy as a result of switching the
reference product for a biosimilar.7
The laws regarding substitution for biosimilars are still
coming into focus, and will vary at the state and federal levels
(see Figure 4).56 However, it is important to keep in mind that
state laws governing substitution will only apply to biosimilars
designated by the FDA as interchangeable—and that has not
been achieved by any biosimilar candidates as of the printing of
this report.56 FDA policies on approval standards for biosimilars
do not address substitution.1, 3 Within multiple state jurisdictions,
there is ongoing legislative activity regarding substitution of
interchangeable biologics with the reference product.56
BIOSIMILARS
LANDSCAPE
Biosimilar Substitution
INTRODUCTION
Determination of Interchangeability
APPROVAL
PATHWAY
Interchangeability
GAME CHANGERS
LOOKING AHEAD
Prior to 2013, no state laws specifically addressed the substitution of biologics.56 See Figure 4 on the next page to see how
U.S. state legislation related to biosimilar substitution has changed since then.
15
As of February 2016, several states have passed legislation with varying stipulations regarding substitution of
interchangeable biologics, even though there are currently no interchangeable biologics on the market.56
While the approval of the first biosimilar has helped to clarify
some aspects of the regulatory, naming, and reimbursement
pathways in the U.S., it is too early to determine its ultimate
impact on the U.S. healthcare system or on the future of the
biosimilar marketplace. MAP BREAKDOWN
As noted previously, the FDA has stated that biosimilar candidates
will be evaluated only against their reference products, and not
against other biosimilars.5, 9 Therefore, it cannot be assumed that
biosimilars are comparable to one another.5
FIGURE 4. STATE LEGISLATION REGARDING BIOSIMILAR SUBSTITUTION IN THE U.S. AS OF FEBRUARY 8, 201656
NH
VT
WA
ND
MT
MA
MN
OR
NY
WI
SD
ID
MI
WY
IA
NE
NV
UT
CA
CO
IL
KS
IN
MO
OK
NM
NJ
WV
DE
VA
SC
AR
DC
Key
Enacted law
GA
AL
No decision has been made
Filed; failed/-adjourned
TX
Bill pending
AK
16
MD
NC
LA
FL
HI
CT
OH
KY
MS
RI
PA
TN
AZ
ME
VI
PR
Source: Adapted from NCSL, 2016
INTRODUCTION
NAMING, CODING, & PAYMENT GUIDANCE
FOR BIOSIMILARS
FDA Draft Naming Guidance
Potential variables and considerations for naming biosimilars
include: 20,58
•
The reference product and all corresponding biosimilars
should have the exact same name
•
All biosimilars should have distinguishable names—
represented by prefixes to the name of the shared core
drug name of the reference product
•
All biosimilars should have distinguishable names—
represented by suffixes to the name of the shared core
drug name of the reference product
•
The number of letters in the prefix or suffix should be
specified, and could either have meaning or be random
GAME CHANGERS
Many stakeholders believe that most biosimilars will be marketed
with unique brand names, at least in the initial development of
the biosimilars market.57 However, brand names are not required,
and prescribers as well as other healthcare providers are not
required to use them. In contrast, non-proprietary names
(sometimes referred to as the United States Adopted Name
(USAN), International Nonproprietary Name (INN), or “active
ingredient name”) are required for all drugs and biologics, and
are often preferentially used in prescribing and health records.
The question has been raised about whether biosimilars should
Pharmacovigilance and ongoing monitoring efforts could be
impacted by the FDA’s final decision on biosimilar naming.
While not all biologic manufacturers and healthcare providers
may have the same perspective, a great number have argued
that assigning biosimilars unique, non-proprietary names is
an important consideration in guarding against inappropriate
substitution and ensuring accurate safety monitoring.58
NAMING, CODING
& PAYMENT
Appropriate naming of a biosimilar may seem, at first glance, to
be a relatively minor concern, but it constitutes a necessary step
for post-market monitoring of biosimilar efficacy and safety,
relative to each other and to the reference product. There are
a number of perspectives on how a biosimilar should be named.
have unique non-proprietary names to ensure that they are
not treated like multisource generic drugs for purposes of
prescription ordering, health records, and pharmacovigilance.58,59
BIOSIMILARS
LANDSCAPE
Developments in 2015 offered some clarity on how key
regulatory agencies plan to accommodate naming and
reimbursement for biosimilars. While many questions
still remain, both the FDA and the Centers for Medicare
and Medicaid Services (CMS) issued guidance in late
2015 that provided more direction on the future of
biosimilars in the U.S.20, 22
LOOKING AHEAD
In August 2015, the FDA issued draft guidance on biosimilar naming.20 In this report, the FDA stated that shared nonproprietary names are not appropriate for all biologic products, and proposed an alternate naming pathway that would
use four-letter suffixes to differentiate between reference products and their biosimilar counterparts.20
17
NAMING, CODING, & PAYMENT GUIDANCE
FOR BIOSIMILARS
Key components of the draft guidance include:
•
•
A proposal that reference products and biosimilars have nonproprietary names that share a core drug substance name
and an FDA-designated suffix that would allow for better
identification of each product.20 This approach would require
manufacturers of reference biologics to retroactively modify
the current name of the reference product to which biosimilars
have been approved. The challenges to manufacturers, other
stakeholders, and systems to implement a new name for
currently marketed biologics are unclear.
Outstanding questions regarding how the FDA plans to approach
naming for reference products and biosimilars that have
been designated as interchangeable.20 For interchangeable
biologic products, the FDA requested feedback from the
public to determine whether the non-proprietary name for
an interchangeable biologic should include a distinguishable
suffix, or whether it should share the same suffix as the
reference product.20 In the latter scenario, should the
FDA designate a previously marketed non-interchangeable
biologic as interchangeable with its reference product, the
name of the biosimilar would then need to be changed to
match that of the reference product.
•
Verification that an identical name would not be required to
facilitate substitution of interchangeable biologics. The FDA
intends to convey interchangeability designations via the
“Purple Book.”60 As of February 2016, state pharmacy laws
permitting substitution of interchangeable biologics refer to
the FDA interchangeability designation and do not require
the products to use the same name.56
In a web-based survey of 401 U.S. pharmacists conducted in
October 2015 by Industry Standard Research on behalf of the
Alliance for Safe Biologic Medicines, 77 percent of respondents
indicated they preferred a suffix that connects the biosimilar to
the product’s manufacturer rather than a suffix with no meaning.61
77%
18
OF RESPONDENTS INDICATED
THEY PREFER A SUFFIX THAT
CONNECTS THE BIOSIMILAR TO
THE PRODUCT’S MANUFACTURER61
INTRODUCTION
Final CMS Reimbursement Provisions for Biosimilars
These policies went into effect on January 1, 2016.22 CMS
generally sets Hospital Outpatient Prospective Payment System
payment policy for biosimilars in alignment with the provisions
for payment in the physician setting.62
*The current federal spending sequester requires all Medicare
government payments to be reduced by 2 percent.63
ONE HCPCS CODE
BIOSIMILAR THREE
LOOKING AHEAD
BIOSIMILAR TWO
GAME CHANGERS
ONE HCPCS CODE
BIOSIMILAR ONE
NAMING, CODING
& PAYMENT
In the payment rule, CMS finalized its proposal for reimbursement
of biosimilar products, confirming that all biosimilar products
of the same reference product will be pooled and combined
into a common Healthcare Common Procedure Coding System
(HCPCS) code.22 The combined HCPCS code will use a weighted
average to determine the biosimilar ASP. The reference product
will continue to have its own HCPCS code and payment amount
and will not be included in the biosimilar ASP calculation.22
For coverage year 2016, all biosimilar products associated
with a particular reference product will be paid under a single
billing code and receive a payment equal to 100 percent of
the weighted average ASP for the biosimilar products, plus a
constant dollar add-on equal to 6 percent* of the reference
product’s ASP.22 The reference product would remain in its own
billing code and continue to be paid 106 percent* of its own
ASP.23 Prior to establishment of an ASP for a biosimilar, CMS will
pay 106 percent* of the Wholesale Acquisition Cost (WAC) of
the biosimilar, not of the reference product.22
BIOSIMILARS
LANDSCAPE
In October 2015, CMS issued its final ruling on Payment for
Medicare Part B Covered Drugs and Biologics for 2016, including
policies for biosimilars.22 Per the guidance, CMS will maintain its
policy standard of reimbursing products according to the current
calculation-based methodology of average sales price (ASP)
plus 6 percent* reimbursement for Medicare Part B covered
drugs and biologics for coverage year 2016.22
ORIGINAL BIOLOGIC
19
GAME CHANGERS
20
INTRODUCTION
GAME CHANGERS
preferred biologic when more biosimilars are approved—
are shown in the figure below and discussed throughout
this report.
BIOSIMILARS
LANDSCAPE
Many of the factors that inform coverage and preference
decisions for biologic medicines, including biosimilars—and
which may ultimately justify a change in an organization’s
RELIABILITY
COVERAGE POLICIES
UNCOVERING THE
UNKNOWNS
LOGISTICS
EDUCATION
GAME CHANGERS
REIMBURSEMENT
BIOSIMILAR
SAFETY
LOOKING AHEAD
21
GAME CHANGERS
COVERAGE POLICIES
Pharmacy vs. Medical Benefit Coverage
The coverage and appropriate utilization of biosimilars may
be influenced by whether a biosimilar is managed through
the pharmacy benefit or through the medical benefit.64 To the
extent that biosimilars and reference products are covered
through a medical benefit, payers will likely face the same issues
regarding utilization management and tracking in the medical
benefit specialty category for biosimilars as they do today for
all biologics. For biosimilars, tracking of safety over time, or
pharmacovigilance, is particularly important in order to better
understand the benefits and risks of these products.4
A prescription drug covered through the medical benefit is
typically administered by a healthcare professional, while a
prescription drug covered through the pharmacy benefit is
typically self-administered by the patient.65 The pharmacy benefit
can include specialty, mail-order, and retail pharmacy, while
drugs covered through the medical benefit may be administered
in a variety of settings (see Figure 5).66
FIGURE 5. COVERAGE OF PHARMACY VS. MEDICAL BENEFITS66
DRUG SPEND
PHARMACY BENEFIT
MEDICAL BENEFIT
SPECIALTY PHARMACY
OUTPATIENT HOSPITAL
MAIL-ORDER PHARMACY
PHYSICIAN OFFICE
RETAIL PHARMACY
HOME INFUSION
AMBULATORY INFUSION
CENTERS
INPATIENT HOSPITAL
Source: Artemetrx. Specialty Drug Management. 2015
22
INTRODUCTION
BIOSIMILARS
LANDSCAPE
In addition, while pharmacy benefit and specialty pharmacy
claims are adjudicated using the National Drug Code (NDC),
drug claims covered under the medical benefit submitted by
medical providers are typically adjudicated using a less specific
Healthcare Common Procedure Coding System (HCPCS) Level
II J-Codes.68 Therefore, tracking use and safety of medical
benefit therapies can be more difficult than tracking pharmacy
benefit therapies. It is reasonable to assume that this challenge
will continue to be true for all biologics, including biosimilars.
Given that CMS has issued final guidance designating that all
biosimilars in a category have a blended code, further issues
could result with tracking use and safety for biosimilars through
the medical benefit channel.
COVERAGE POLICIES
Payers may stipulate that specialty drugs be predominately
dispensed through contracted specialty or local retail pharmacies.64
Prescription drugs dispensed through retail, mail order, or specialty
pharmacies are typically adjudicated online. However, this is not the
case for prescription drugs covered through the medical benefit,
which are adjudicated retroactively and paid to the medical office,
clinic, or other provider on a buy-and-bill basis.64
UNCOVERING THE
UNKNOWNS
Payers often use specialty pharmacy dispensing for prescription
drugs with particular characteristics—such as high cost, special
handling requirements, special storage/preparation, or complex
administration. Biologics, including biosimilars, are typically
considered specialty drugs.67
LOOKING AHEAD
To help manage the utilization of drugs covered under the medical
benefit, payers may develop coverage and reimbursement
policies and implement them prior to authorization.64
23
GAME CHANGERS
Patient Population Size
“…each drug, as it comes, will have to be evaluated individually based on the patient population that it
impacts and the demographic of the patients that we’re treating.”70 – THE EDITORIAL COUNCIL
Drugs used to treat large patient populations are the main drivers
of cost in the healthcare system and represent a promising area
for savings.63 Therefore, differences in the projected patient
population size for a given biosimilar will likely weigh into
the decision of whether a particular agent will be included
on a formulary.63
PRODUCT CLASSES THAT MAY BE IMPACTED BY A BIOSIMILAR ENTRY INTO THE U.S. MARKET 71
ESTIMATED 2014 U.S. SALES ($M) BY PRODUCT
$0
$4,000
$8,000
$12,000
$16,000
$20,000
$24,000
Anti-TNFs
G-CSFs
ESAs
IFNs
Anti-CD20s
Anti-HER2s
Anti-VEGFs
Anti-EGFRs*
* Evaluated anti-EGFR monoclonal antibodies only
Anti TFNs, anti-tumor necrosis factors; ESAs, erythropoiesis-stimulating agents, Anti-CD20s, anti-cluster of d
ifferentiation 20s; IFNs, interferons; Anti-HER2s, anti-human epidermal growth factor receptors; Anti-VEGFs,antivascular endothelial growth factors; G-CSFs, granulocyte-colony stimulating factors; Anti-EGFRs,anti-epidermal growth factor receptors
Source: Amgen, Data on File. IMS Health National Sales Perspective (NSP) Audit October 29 2015
24
INTRODUCTION
Formulary: Drug Formulary Assessment, Fit, & Policies
As biosimilars may be treated as specialty drugs (as some
biologics are),67 there may be challenges incorporating them into
the current tiering system. Questions may arise as to whether
or not to place biosimilars on a currently existing tier, or to
create a new tier for a specialty drug that is also a biosimilar
(see Figure 6).76
UNCOVERING THE
UNKNOWNS
COVERAGE POLICIES
As a result, appropriate utilization of biosimilars, both overall
and within particular therapeutic categories, will be determined
by multifaceted decisions by payers, patients, integrated
delivery networks (IDNs), hospitals, and employers. For example,
some payers may rank potential savings higher than consumer
choice when it comes to assessing biosimilars.73 On the other
hand, some self-insured employers may be more concerned
about the impact on their company’s reputation and employee
morale if employees feel they are being “forced” into lower-cost
treatments.
An organization’s formulary is developed and maintained by its
Pharmacy & Therapeutics (P&T) committee, which appraises,
evaluates, and selects drugs for the formulary. The vast majority
of coverage plan sponsors specify a two-, three-, four-, or highertiered formulary, and then structure their coverage options in
accordance with these tiers.74 For drugs covered under the
pharmacy benefit, traditional tiering is based on several drug
characteristics, including whether a drug is available from
multiple sources or only from a single source, the drug’s net cost,
and its specialty designation.75 This structure may now need to
be adapted to accommodate biosimilars.
BIOSIMILARS
LANDSCAPE
Realizing the savings, however, involves a complex set of
considerations. For example, assessment of a biosimilar’s fit within
a formulary design requires not only an analysis of potential savings,
but also of current clinical guidelines and practices, societal factors
and behaviors, operating costs, logistical implications, physician
and patient acceptance, and the likelihood of clinical use and
adoption.72 When faced with these multiple considerations,
stakeholders may feel that the potential benefits of adding a
biosimilar to a formulary may not justify the required effort and
resources to enact the change.
NON-PREFERRED BRAND TIER ($$$)
Typically the highest cost sharing. Non-preferred brands have generally not been found to be any more cost effective
than available generics, preferred brands, or over-the-counter drugs.
PREFERRED BRAND TIER ($$)
Typically a slightly higher cost sharing than generics. Preferred brands have been proven to be safe and effective,
and are favorably priced compared to other brand drugs that treat the same condition.
Typically the most affordable cost sharing. The active ingredient in a generic
drug is chemically identical to the active ingredient of the corresponding brand.
LOOKING AHEAD
GENERIC TIER ($)
PATIENT COST SHARING ($)
FIGURE 6. FORMULARY TIERS FOR DRUG DISPENSING77
Source: Avalere. Value Based Formulary Design. 2015
25
GAME CHANGERS
Formulary decision makers, including P&T committees, may consider the following when evaluating a biosimilar: 72, 78, 80
PRODUCT: Clinical data; evidence-based reviews and guidelines; indications, labeling, immunogenicity,
interchangeability, pharmacovigilance requirements; preparation, administration, and storage requirements
MANUFACTURER: Supply reliability and history of shortages; supply chain security and anti-counterfeit measures;
patient assistance and reimbursement support
COMMERCIAL & GOVERNMENT PAYERS: Financial impact; sponsor (i.e. commercial, Medicare, Medicaid); coverage
and reimbursement policies needed to support, transition from a reference product to a biosimilar; information
and claims system; provider acceptability; support programs, including education, for providers and patients; costs
associated with potential for drug shortages, for monitoring the response to biosimilar treatment, for monitoring
of therapeutic interchange, and cost impact of patient-assistance programs; negotiation and influence of bundled
contracting approaches; cost impact of patient-assistance programs
PROVIDER: Clinical studies and evidence-based review; electronic medical record and medication system; educational
requirements for staff, providers, and patients; administration-related costs; economic considerations, including 340B;
costs for pharmacovigilance; costs associated with potential for drug shortages; costs for monitoring the response to
biosimilar treatment
PATIENT: Acceptability (related to factors such as therapeutic category, therapeutic vs. supportive care, acute vs.
chronic therapy, and new vs. continuing therapy); disease severity and comorbidities; education; cost share and
savings; adherence.
EMPLOYER / PURCHASER: Employer purchasers may provide guidance, or potentially overrule coverage decisions.
WHAT TO EXPECT NEXT
As we look to the future, it is unclear how payers will manage
biosimilars, whether through the pharmacy benefit or through the
medical benefit. Furthermore, we may see more direct contracting
26
by employer purchasers with IDNs.79 We expect to see biosimilars
within formularies, but the placement within the formulary, whether
to an existing tier or creating a new tier, is undetermined.
INTRODUCTION
EDUCATION
As of March 2016, only one biosimilar has been marketed
for use in the U.S.14 This limited exposure to the functional
and operational aspects of biosimilars may contribute to why
patients, physicians, pharmacists, and allied health workers
have various levels of awareness and familiarity with biosimilars
today.72 Several surveys show that stakeholders have one
thing in common: the belief that education about biosimilars
is essential.61, 81
BIOSIMILARS
LANDSCAPE
Informed Choice for Physicians
“If you speak to physicians, you’ll hear the term ‘financial toxicity’ 49 when the physician has identified
the appropriate therapy for their patient, the problem is the patient may not be able to afford it or have
access to it.”70 – THE EDITORIAL COUNCIL
UNCOVERING THE
UNKNOWNS
EDUCATION
LOOKING AHEAD
27
GAME CHANGERS
The use of any biologic in medical practice could be impacted
by the treatment setting (medical office/clinic, home, hospital,
or long-term care facility), chronic versus acute use, and
its indication. Introducing a biosimilar option adds to the
complexity of this choice. In addition to considering the
potential savings that a biosimilar may (or may not) present to
the patient, a provider may have other questions or concerns
related to biosimilars:
QUESTIONS
28
•
Does a biosimilar have all the indications of the reference product?;72
•
Were the products’ indications approved through extrapolation or through clinical trials?;72
•
Is the biosimilar as safe and efficacious as the reference product?; 82
•
Is the dosing and administrative device equivalent for the biosimilar and the reference product?;80, 83
•
Has the biosimilar been designated as interchangeable by the FDA?;80
•
Are formulary barriers in my therapeutic choice for my patients?;72
•
Are there reimbursement support and other programs available for my patients?;80
•
How does the site of care or payment model impact reimbursement (e.g., is it retail or buy-and-bill)?;64
•
Is my patient drug-naive to treatment options for the molecular target?;72
•
How do I track and trace which version of the molecule will be dispensed?;72
•
How comfortable is my patient with the use of a biosimilar?;84
•
Will providers need to educate the patient about drug administration devices or managing injection site discomfort?72, 85
INTRODUCTION
BIOSIMILARS
LANDSCAPE
UNCOVERING THE
UNKNOWNS
EDUCATION
expected reliability to deliver a consistent supply of the selected
biologic to the list.72 Navigating this long list of considerations
may require a significant amount of education for a physician to
make a truly informed choice.72
LOOKING AHEAD
Medical history is also a factor. In many cases, patients with
chronic disease may be stabilized on a particular product and
the provider may choose to maintain the patient on that product.
This, too, could influence a provider’s decision to prescribe
a biosimilar.84 Finally, one can add a manufacturer’s known or
29
GAME CHANGERS
“Integrated Delivery Networks [IDNs] have been spending the last three years prepping everybody for
biosimilars because we knew physician engagement was going to be the key driver to making this [utilization
of biosimilars] successful. And if we start educating after it [biosimilar] has been released, it’s too late.” 70
– THE EDITORIAL COUNCIL
Providers
According to recent studies, pharmacists and physicians want
additional and in-depth education about biosimilars.61, 82 Based
on the key roles both pharmacists and physicians play in the
treatment and care of patients, ensuring these key stakeholders
are educated on the myriad of topics related to biosimilars may
be one of the pivotal factors to support appropriate utilization
of a biosimilar.61, 82
30
In March 2015, QuantiaMD conducted a survey of nearly 300
primary care physicians and specialists in the therapeutic
areas where biosimilars are most concentrated
—including
endocrinology, gastroenterology, hematology, infectious disease,
oncology, nephrology, neurology, and rheumatology—and found
that prescribing specialists have a general level of awareness
about biosimilars.82 However, the awareness level drops sharply
as they are asked about specifics as seen in Figure 7.82
INTRODUCTION
FIGURE 7. PHYSICIAN INTEREST IN LEARNING ABOUT BIOSIMILARS82
0%
25%
50%
75%
100%
ARE FAMILIAR WITH THE
TERM “BIOSIMILAR”;
78%
53%
38%
ALREADY PRESCRIBE
BIOLOGICS;
ARE AWARE THAT THE FIRST BIOSIMILAR
WAS APPROVED BY THE FDA;
ARE AWARE OF A BIOSIMILAR UNDER CONSIDERATION FOR APPROVAL
THAT WOULD BE RELEVANT TO THEIR PATIENT POPULATION; AND
CAN NAME A BIOSIMILAR UNDER
CONSIDERATION FOR APPROVAL.
UNCOVERING THE
UNKNOWNS
33%
BIOSIMILARS
LANDSCAPE
60%
Source: QuantiaMD. Physician Biosimilar Survey. 2015
ONLY
35%
OF RESPONDENTS SAID THAT THEY
HAD A COMPLETE UNDERSTANDING
OF BIOSIMILARS61
EDUCATION
Similar results were observed in a separate survey of 401
pharmacists, sponsored by the Alliance for Safe Biologic
Medicines in October 2015: only 35 percent of respondents
said that they had a complete understanding of biosimilars.61
Of particular note, hospital pharmacists were more likely to be
“very familiar” with biosimilars than were retail pharmacists (44
percent vs. 23 percent, respectively).61
It is possible that knowledge of biosimilars will increase since
these surveys were completed, given that the first biosimilar was
launched in September 201521 and that the FDA provided some
new draft guidances as well as finalized other previous draft
guidances that year.18
LOOKING AHEAD
31
GAME CHANGERS
In February 2016, in an effort to help educate providers on
biosimilars, the FDA introduced a free Continuing Education
Course for healthcare professionals—titled, FDA Overview of
Biosimilar Products—to help strengthen providers’ knowledge
and understanding of biosimilars and interchangeable products.87
However, there are still opportunities to gain further clarity on
some biosimilar topics. As of March 2016, the FDA has yet to
issue final guidance on the exact amount and type of information
required in a biosimilar’s labeling, which may raise several
questions:69
QUESTIONS
•
Should the labeling disclose data from the clinical trials that compared the biosimilar with the reference product?
•
Should the labeling briefly describe the FDA’s basis of approval for a biosimilar to a specific reference product?
•
Should the labeling disclose whether or not the FDA has designated the product as interchangeable with the reference product?
•
Should the labeling disclose if any indications or conditions of use of the reference product are not approved for the biosimilar?
•
Should a clinician be made aware that the data presented for extrapolated indications were not actually based on clinical testing
of the biosimilar?
Labeling for the first biosimilar product approved by the FDA
discloses none of the above information.88 While formulary
directors may be able to obtain some desired details not
disclosed in a biosimilar’s label from FDA’s approval history or
from an Academy of Managed Care Pharmacy (AMCP) dossier
submitted by the manufacturer, that information may not be as
accessible to patients or providers who may want to learn more
about a product to make more informed treatment decisions.89
“For [P&T committees] trying to understand the clinically meaningful differences between the biosimilar
and its reference product, it would be helpful to have that information available on the product label.
This is where I would like to see the clinical trials section or others replicated into formal biosimilars labeling
structures.” 70– THE EDITORIAL COUNCIL
32
INTRODUCTION
Patients
The primacy of the patient/physician relationship is reflected
in a 2015 survey by the Global Healthy Living Foundation.84 Of
the 177 arthritis patients surveyed, a majority of respondents
stated that the decision to prescribe a biologic should remain
in the hands of the patient and his or her physician, while only
2 percent of respondents felt payers should make this decision
(see Figure 8.).84
BIOSIMILARS
LANDSCAPE
One should expect that patients want to make completely
informed decisions regarding the choice of which biologic to
use - a biosimilar, or its reference product. Patients may receive
their information regarding healthcare from a number of sources,
but physicians often remain their primary point of reference. This
has marked implications for patient education and utilization of
biosimilars, as patients may mirror or adopt their physician’s
point of view.
FIGURE 8. PATIENT PREFERENCE ON MEDICATION
CHANGES84
90
%
UNCOVERING THE
UNKNOWNS
7%
Physicians
2%
Pharmacists
Payers
EDUCATION
WHAT TO EXPECT NEXT
payers and providers as more payers have increasing influence
in financial decisions in regard to biosimilars. To help alleviate
this, it will be important for payers and manufacturers to help
facilitate the additional education of physicians, pharmacists,
and patients on the science supporting the use of biosimilars.72
LOOKING AHEAD
Evidence shows that there is need for additional patient
education around the appropriate use and considerations
associated with biosimilars. It will be important for physicians
to have sufficient knowledge and experience with biosimilars
to speak comfortably with their patients about these agents. To
this end, we anticipate there may be potential friction between
Source: Global Healthy Living Foundation. Patient
Perspectives on Medication Switching for NonMedical Reasons. 2015
33
GAME CHANGERS
“I really just cannot stress enough how difficult it can be to make changes within our electronic medical record
[EMR] infrastructure. One small change when you’re looking at a drug formulary and [you have to weigh] the
EMR infrastructure changes across your healthcare organization…And if we’re going to save a relatively small
amount, it’s not worth it, at all.” 70 – THE EDITORIAL COUNCIL
LOGISTICS
Payer and provider organizations may need to address logistical
considerations resulting from the addition of a biosimilar to their
inventory and data management systems.
Of particular importance is the need to reprogram and adapt
existing information technology (IT) systems to accommodate
the inclusion of biosimilars into hospital/Integrated Delivery
Network (IDN) formularies. This endeavor will likely involve
associated changes in the electronic medication-administration
systems (eMARs), adapting Electronic Medical Records (EMRs),
reprogramming to support preference for a certain product,
and making the changes needed to support various coding and
pricing schemes.72 Evaluation of the potential costs associated
with making needed system changes may be compared to
potential savings to help determine if a change will be beneficial
in the short and long term.72
An additional logistical consideration is managing different
pricing schedules for inpatient and outpatient pharmacies within
the same health system. This may be a challenging problem for
health systems that use the same EMRs for 340B hospitals as
well as for other pharmacy fulfillment mechanisms that are not
34
supported by federal discount programs, such as commercial
direct mail, purchases by pharmacy benefit managers, HMOs,
mail-order pharmacies, insurers, hospitals, and clinics.90 Many
health systems today include hospitals, home health agencies,
hospices, stand-alone clinics, and physician practices in order to
provide a continuum of care as an IDN.91 An IDN’s operations may
be divided between inpatient and several types of outpatient
treatment settings as well as commercial and government
operations.91 As a result of this complexity, IT standardization
and integration across settings may be challenging.
From the financial perspective, sites within a single healthcare
system that qualify as 340B covered entities can obtain federally
mandated “ceiling price” discounts for covered outpatient drugs,
while other sites that are not 340B-eligible usually pay a higher
net price.92 Keeping track of pricing differences for a single
product could be a significant burden in a complex healthcare
system which may have ongoing data integration efforts. Since
biosimilars may present another price point to an already
established treatment option, differential pricing could be even
more complex if biosimilars were added to a formulary.
INTRODUCTION
“340B pricing may hamper the adoption of biosimilars with 340B organizations. This delay will stem from the
fact that there would be no historical discount set for biosimilar products to base a 340B or Medicaid price
off of.” 70 – THE EDITORIAL COUNCIL
340B Health is a membership organization of more than
1,100 hospitals and health systems, both public and private
nonprofits, throughout the U.S. that participate in the
340B Drug Pricing Program.93 It is managed by the Health
Resources and Services Administration (HRSA).
OF HOSPITALS IN
THE U.S. ARE
PART OF THE
340B PROGRAM94
In August 2015, HRSA issued proposed guidance
for governing policies related to the 340B Drug
Pricing Program.44
•
Covered entities include six categories of hospitals:
disproportionate share hospitals, children’s hospitals, and
cancer hospitals exempt from the Medicare prospective
payment system, sole community hospitals, rural referral
centers, and critical access hospitals.90
•
340B is a growing sector: Covered entities and their
affiliated sites spent more than $7 billion to purchase
340B drugs in 2013, three times the amount spent
in 2005.90
•
Approximately 40 percent of all U.S. hospitals participated
in 340B in 2015.94
•
Ceiling prices for 340B drugs are not publicly disclosed.
However, it has been estimated that 340B hospitals
receive discounts on the average sales prices of
medications ranging from 15 to 60 percent.90, 95
•
Medicare Part B pays for certain 340B treatments, such
as biologic drugs used to treat cancer and rheumatoid
arthritis, at the same rate as 340B hospitals and non-340B
hospitals. It does this despite the fact that 340B hospitals
are able to obtain those treatments at a discount.90
LOOKING AHEAD
•
LOGISTICS
40%
Quick facts about the 340B Program:
UNCOVERING THE
UNKNOWNS
The 340B program requires drug manufacturers to sell
outpatient drugs at a discount to safety-net providers
serving high numbers of low-income Medicare, Medicaid,
and Supplemental Security Insurance patients. Congress
created the program to allow these providers to “stretch
scarce federal resources as far as possible, reaching more
eligible patients and providing more comprehensive services.”
Savings from the program help fund free and low-cost
medications as well as HIV/AIDS, diabetes, cancer, dental, and
primary care clinics that serve our most vulnerable citizens.93
BIOSIMILARS
LANDSCAPE
THE 340B DRUG PRICING PROGRAM
35
GAME CHANGERS
WHAT TO EXPECT NEXT
Support for biosimilar utilization may pose challenges to
existing IT systems and processes across the healthcare industry,
including the need for customization of EMRs and eMARs.72
In addition, there is the potential need to develop a standardized
approach to pricing schedule, especially for health systems
participating in the federal 340B Drug Pricing Program.
RELIABILITY
36
40%
FIGURE 9. REPORTED CAUSES OF DRUG
SHORTAGES, 2011-2013 98
%
30
Quality problems
Manufacturing delays
and capacity issues
Product
discontinuation
Active pharmaceutical ingredient
(API) or non-API component issue
Increased demand
12
6%
%
Loss of manufacturing
site or site change
9%
As more manufacturers plan to enter the biosimilar market, it will
likely become increasingly important for stakeholders to have
an understanding of each company’s manufacturing capabilities,
quality assurance process, reputation for consistent supply, and
plans for avoiding shortages.72 In choosing one product over
another, a P&T committee may evaluate a manufacturer’s reliability,
safety, and quality control history as well as its safeguards to
ensure manufacturing capacity and dependability.80 It may also
be important to evaluate a manufacturer’s ability to institute
procedures to ensure a steady product supply, including
backup or multisite manufacturing capabilities to accommodate
unexpected disruptions at the primary manufacturing site.80
3%
Drug shortages can have a dramatic fiscal impact on hospitals
because shortages could increase the cost of delivering patient care.
For example, when a drug shortage occurs, the cost of acquiring
alternative drug supplies might incur costs if re-contracting is
required. 96 Drug shortages can also lead to a substantial number
of treatment changes. Physicians report that in some cases,
when a patient’s treatment is modified due to supply problems,
the available alternatives have a weaker evidence base than the
medications in shortage.97 Concerns about reliability of supply are
well-founded based on the generic manufacturing industry’s history
with the production of sterile injectables, which is a segment of the
pharmaceutical market that has suffered numerous shortages over
the years—largely due to quality control issues (see Figure 9).98
An economic analysis suggests that shortages of injectable drugs
may also be associated with inadequate reimbursement for
multisource drugs predominantly covered by Medicare,99 a risk
factor that also might apply in the future for certain classes
of biosimilar products.
Source: United States Government Accountability Office. Drug Shortages. 2014
INTRODUCTION
MEASURING THE VALUE OF BIOSIMILARS70
PETER NEUMANN, SCD
Director, Evaluation of Value and Risk in Health,
Tufts Medical Center
RELIABILITY &
MEASURING VALUE
In considering the value of biosimilars, there may be residual
questions at time of launch that can only be answered through
additional experience in clinical practice. The biosimilar will
have been shown to have no clinically meaningful differences
in its approved indications, but it may not be licensed for
Going forward, there is a need for more evaluation. Cost
effectiveness analysis in which costs and health outcomes
are measured and compared to alternative strategies is one
tool to help. Research would also be useful on the impact
of various coverage and formulary policies that incorporate
biosimilars. Finally, there will be an important role for
education – of patients, physicians, pharmacists – around all
of these issues.
UNCOVERING THE
UNKNOWNS
Broadly speaking, estimating the value of interventions
means judging the costs and health outcomes they generate
compared to a relevant alternative. In practice, it means
weighing multiple dimensions, including the quality of clinical
data, the magnitude of treatment effects, the likelihood of
adverse events, and a product’s overall cost-effectiveness
and budget impact.
There are uncertainties in each
estimation step. Moreover, judgments about how to weight
various dimensions vary within and among interested parties,
including patients, physicians, employers, and payers.
all of the reference product’s indications. Biosimilars may
require a slightly different dose (for titrated products), or
may differ in terms of certain patients’ ability to stay on the
therapy long term. Considerations of value must consider
whether a lower price is worth the potential differential in
these attributes.
BIOSIMILARS
LANDSCAPE
Achieving better value is the central focus of American
health policy debates. By definition, biosimilars should help
in the pursuit. They promise similar health outcomes and
cost savings. However, whether biosimilars deliver on the
promise hinges on several considerations.
Member of the Editorial Council
37
LOOKING AHEAD
“ There are a lot of challenges to consider before jumping to adopt a biosimilar. We have been so heavily
impacted by drug shortages at our organizations that if we have a good stable supply of a very necessary
product to treat our really sick patients, we’re going to stick with that until we can truly ascertain whether
or not the biosimilar is going to be supplied in the quantities that we need it.” 70 – THE EDITORIAL COUNCIL
GAME CHANGERS
CONTRACTING
The availability of biosimilars may impact contracts among
payers and IDNs, wholesalers, group purchasing organizations
(GPOs), and manufacturers by presenting several new
considerations to evaluate.
Stakeholders may negotiate discounts with biosimilar
manufacturers in a similar manner as they do with the
manufacturers of reference products. Having biosimilars on the
market that are FDA-designated as interchangeable may afford
payers greater leverage when negotiating with manufacturers
that have biosimilars that have not been
designated as interchangeable with the same reference product.
Furthermore, a manufacturer may earn additional negotiating
power should it have the first interchangeable biosimilar in a multibiosimilar marketplace.7 In fact, by statute, an exclusivity period
will be granted should a biosimilar receive an interchangeable
designation by the FDA, and if it is the first to receive that
designation, no other biosimilar to the same reference
product may receive an interchangeable designation by
the FDA.7 As of March 2016, there are no interchangeable
biosimilars in the U.S. market.
“One consideration when contracting for a biosimilar, is that the reference product may have a high level of
support from healthcare providers, which may make it more difficult to drive adoption, especially for patients
already on established therapies.” 70 – THE EDITORIAL COUNCIL
38
both marketing biologics and developing biosimilars, the
contracting environment is expected to become more complex
as new biosimilars come to market.103
PAYER MERGERS
VALUE-BASED
CONTRACTING/REIMBURSEMENT
UNCOVERING THE
UNKNOWNS
LANDSCAPE
THE PACE OF ENTRANTS
AND NUMBER OF BIOSIMILAR
COMPETITORS
BIOSIMILARS
LANDSCAPE
340B PRICING/CONTRACTING
REBATES
CONTRACTING
INTRODUCTION
In recent years, we have witnessed an increase in collaborations,
mergers, and acquisitions among pharmaceutical companies
looking to expand their portfolios into biosimilars.100, 101, 102 As the
makeup of biosimilar manufacturers changes with manufacturers
MULTI-STATE IDNS
PRICING CAPS
BUNDLED PAYMENTS
BIOSIMILAR MERGERS
CONTRACTING
DIFFERENTIATED BIOSIMILARS
(Extrapolation, Number of indications, Interchangeability,
Varying clinical study designs)
WHAT TO EXPECT NEXT
biosimilar manufacturers continues to shape through mergers
and collaborations as well as the potential negotiating power
both manufacturers and formulary decision makers may
have should the FDA begin to approve biosimilars with an
interchangeable designation.
LOOKING AHEAD
The biologics marketplace has become sensitive to shortages in
recent years. Payers, IDNs, and providers may make their degree
of confidence in a manufacturer’s ability to avoid shortages a
key consideration when evaluating their preferences among
multiple biosimilars as well as the reference product.80 The
contracting process will likely evolve as the complexion of
39
GAME CHANGERS
REIMBURSEMENT
Biosimilars bring the opportunity for savings to a healthcare
system that is constantly searching for efficiencies while
simultaneously aware of the need to preserve incentives that
will reward future innovation. Across Medicare program Parts A
(inpatient hospital), B (physician office and outpatient hospital),
C (Medicare Advantage), and D (prescription drug benefit),
prescription drugs totaled 19 percent of overall Medicare
programming spend in the U.S. in 2013.104 Part D represented
57 percent of Medicare drug and pharmacy spending
(see Figure 10).104
FIGURE 10. MEDICARE PROGRAM SPENDING, 2013 104
COMPONENTS OF MEDICARE DRUG
AND PHARMACY SPENDING
57
%
MEDICARE PROGRAM SPENDING=
$574 BILLION
Drugs and pharmacy
Part D
%
12
Part A and B
services delivered
in Medicare Advantage
All else
Inpatient hospital
11%
19%
Physician
and supplier
Other
81%
Outpatient
hospital
%
10
40
5%
5%
The reimbursement landscape continues to change, especially
in light of CMS’ finalized Medicare program reimbursement
provisions22 and the Part B drug payment model demonstration
Source: Schmidt R, et al. Medicare Drug Spending. 2015
program that was proposed in March 2016.105 These guidelines
may influence not only reimbursement incentives, but also
appropriate use and understanding of biosimilars.
INTRODUCTION
CMS Guidelines for Biosimilar Coverage
will be paid at 100 percent of the biosimilar’s own ASP, plus 6
percent* of the ASP for the reference product.22 Prior to ASP
establishment for a biosimilar, CMS will pay 106 percent* of WAC
of the biosimilar (not of the reference product) until ASP can be
used for payment.19
BEFORE ASP IS ESTABLISHED FOR BIOSIMILARS
ONCE ASP IS ESTABLISHED FOR BIOSIMILARS
6%* OF
WAC OF BIOSIMILAR
6%* OF
ASP OF REFERENCE PRODUCT
WAC OF BIOSIMILAR
ASP OF BIOSIMILAR
+
UNCOVERING THE
UNKNOWNS
+
BIOSIMILARS
LANDSCAPE
The Medicare program pays for most Part B drugs at a prospective
rate of ASP plus 6 percent which, since 2013, has been subject
to a 2 percent reduction due to sequestration.22, 63 In order to
incentivize physicians to prescribe biosimilars, CMS stipulated
that once ASP is established for a biosimilar, CMS reimbursement
Payment for a biosimilar is based on ASP of all biosimilar products included within the same HCPCS code.22
In March 2016, CMS announced a proposal for a two-phase
payment model for Part B drugs that would test whether
alternative drug payment designs will lead to a reduction in
Medicare expenditures.105
REIMBURSEMENT
Part D plans must cover generic and brand name prescription
drugs, including biologicals licensed under section 351 of the
Public Health Services Act, that are generally needed by Medicare
recipients for treatment of medically accepted indications.107 Part
D drug plan formularies must include at least two drugs from
each drug category or class unless only one drug is available for
a particular category or class, or only two drugs are available but
one drug is clinically superior to the other.107
LOOKING AHEAD
CMS issued guidelines in 2015 with respect to the coverage
of biosimilars and clarified that the payment amount for a
biosimilar biological product is based on the ASP of all biosimilar
products included within the same billing and payment code.22
This decision has proven to be controversial. During a February
2016 hearing of the House Energy & Commerce Subcommittee
on Health Biosimilars, House and Senate Members voiced their
concerns and opposition to CMS’ policy to group and issue
multiple biosimilars under the same J-code (the most commonly
used HCPCS codes) for Medicare reimbursement purposes.106
Many argued this proposed payment policy would not provide
the right incentives for manufacturers to invest in further trials
for additional indications, subsequently reducing the number of
biosimilar products available in the U.S. market.106
*The current federal spending sequester requires all Medicare
government payments to be reduced by 2 percent.63
41
GAME CHANGERS
CMS Guidelines for Biosimilar Coverage
The CMS guidance notes that biosimilars “may provide
Part D sponsors with new products that create formulary design
options to help control costs while still ensuring beneficiaries
have access to the medications they need.”17
•
“Because biosimilars are not interchangeable with the
reference biological product, CMS expects that Part D
sponsors’ Pharmacy and Therapeutics (P&T) committees
will review newly approved biosimilars in accordance with
section 30.1.5 of Chapter 6 of the Medicare Prescription Drug
Benefit Manual.”
The guidelines include:17
•
“Biosimilars may be added to plan formularies at any time as
a formulary enhancement.”
•
“Biosimilars do not meet the CMS definition of a generic drug
…or the… definition of a multiple source drug.”
•
“For the purposes of Part D transition supply and notice
requirements, biosimilars and the reference biological
product should be treated like different products.”
•
“…biosimilars are non-applicable drugs for purposes of
establishing coverage gap cost sharing under the basic
Part D benefit, and are not discounted or otherwise subject
to (Coverage Gap) Discount Program requirements.”
A 2011 Amgen-sponsored report from Milliman observed “If CMS
does not require the biosimilar manufacturer to comply with the
50 percent discount (i.e., the Coverage Gap Discount Program),
since it applies only to brand-name drugs, then the [reference]
42
biologic price would be more competitive with the biosimilar for
the Medicare-eligible population in the coverage gap. Thus, the
senior population and Medicare Part D may indirectly impact the
biosimilar pricing in the commercial sector.” 108
INTRODUCTION
Compared to Medicare, CMS’ approach to how they classify
biosimilars is different when it comes to Medicaid services.
According to a Medicaid Drug Rebate Program Notice issued to
participating drug manufacturers in March 2015, State Medicaid
programs were instructed that biosimilars should fall within the
definition of single source drugs in the Medicaid Drug Rebate
program.16 Furthermore, states may consider the total rebates
for reference biological products as well as those that have
been determined to be biosimilar to, or interchangeable
with, reference biological products in their determination of
preferred drugs lists consistent with the requirements for prior
authorization programs.16
BIOSIMILARS
LANDSCAPE
FIGURE 11. CLOSING THE COVERAGE GAP 109
REFERENCE PRODUCTS
GENERICS / BIOSIMILARS
45%
5%
40%
10%
35%
15%
30%
20%
25%
25%
50%
50%
50%
50%
2016
2017
2018
2019
2020
0%
BENEFICIARY
PLAN
MANUFACTURER
58%
51%
44%
37%
25%
42%
49%
56%
63%
75%
2016
2017
2018
2019
2020
REIMBURSEMENT
50%
% CONTRIBUTION OF TOTAL DRUG COSTS
100%
UNCOVERING THE
UNKNOWNS
% CONTRIBUTION OF TOTAL DRUG COSTS
100%
0%
Source: Adapted from Medicare Rights Center. Closing the Doughnut Hole. 2014
WHAT TO EXPECT NEXT
Over time, payers will actively learn, both clinically and
economically, where the opportunity of biosimilars can meet
the ongoing reality of the U.S. healthcare system, and will likely
continue to adjust reimbursement mechanisms accordingly.
LOOKING AHEAD
Reimbursement for biosimilars will likely be shaped by payers
and providers as is the case with branded, generic, and specialty
medications. Stakeholders are expected to strive to maximize
biosimilars’ cost effectiveness and value, while remaining
sensitive to patient and provider perceptions and needs.63
43
GAME CHANGERS
SAFETY
With more biosimilars expected to launch in the U.S. market in
the next several years, experts have stressed the importance of
tracking the safety of biosimilars through pharmacovigilance.110,111
A core principle of pharmacovigilance is traceability, the
ability to identify each medical product and link it back to
its
manufacturer.112 It is necessary to differentiate between
the biosimilar(s) and the reference product to ensure that
adverse event reports associated with a specific biologic
are not inappropriately associated with another biologic112—
either the reference product and/or among one or more of its
biosimilars.112, 113 In the U.S., it has been found that medication
orders captured in patients’ EMRs can help validate previously
reported Adverse Event Reports (AERs), and detect new ones.114
Consequently, it is important that the healthcare professionals
prescribing, dispensing, and administering biologic medicines,
including biosimilars, have a clear understanding of which
products are reference products and which are biosimilars, and—
if there is more than one biosimilar available for a reference
product—which biosimilar is being given to a specific patient.
During the February 2016 hearing of the House Energy &
Commerce Subcommittee on Health Biosimilars, a CMS
representative discussed processes they have put in place to
address this issue: 106
“We [CMS] implemented a requirement for claims for
biosimilars to include a modifier that identifies the
manufacturer of the specific product...This will allow
us and others to track which specific biosimilars a
beneficiary receives.”
- Sean Cavanaugh, Deputy Administrator and Director
of the Center for Medicare, CMS
44
INTRODUCTION
ENOXAPARIN CASE STUDY: EXAMPLE OF INADEQUACIES OF CURRENT SYSTEMS FOR
ACCURATE PHARMACOVIGILANCE113
ENOXAPARIN ACTIVE SURVEILLANCE
Administrative claims databases
Useful for answering specific questions
BIOSIMILARS
LANDSCAPE
•
•
FINDINGS:
Pharmacy Benefit
• 33% of unit volume
• Using pharmacy claims to identify
• Products readily identifiable via NDC
ENOXAPARIN PASSIVE SURVEILLANCE*
•
•
Reports submitted to the FDA or manufacturers
Used to detect new safety signals
UNCOVERING THE
UNKNOWNS
Medical Benefit
• 67% of unit volume
• Using institutional and medical claims to identify
• Products have a shared code and cannot be uniquely
identified
FINDINGS:
• Using FDA AE database to identify
• 26% ambiguous AE reports (generic name only)
• Identification of AE reports to brand or generic
manufacturers did not track to unit volume share
* Includes both Pharmacy and Medical Benefit
4%
SAFETY
Other
Sandoz
Winthrop
40%
Identifiable to Sanofi
6%
Identifiable to a specific generic
Sanofi
50%
Not identifiable
26%
LOOKING AHEAD
69
%
5%
UNIT VOLUME SHARE
ADVERSE EVENT REPORTS
Source: Adapted from Grampp et al. ASHP. 2014
45
GAME CHANGERS
This is vital for both pharmacovigilance purposes as well as to
ensure that non-interchangeable biologics are not inappropriately
substituted for reference products. As the FDA states in its Draft
Guidance on biosimilar naming in August 2015:20
“By differentiating among biological products that have not been determined to be interchangeable, the goal of this
naming convention is to help minimize inadvertent substitution. Inadvertent substitution may lead to unintended
alternating or switching of biological products that have not been determined by FDA to be interchangeable.
This naming convention may also facilitate pharmacovigilance for multiple biological products containing related
drug substances when other means to track a specific dispensed product are not readily accessible…”
- U.S. FDA. Guidance for Industry: Nonproprietary Naming of Biological Products. Draft Guidance. 2015
Some experts believe that International Nonproprietary Names
(INNs), while useful for tracing the safety of multisource drug
classes, are insufficient for pharmacovigilance of biosimilars
without the addition of a brand name or the manufacturer’s
name.112 Naming of biosimilars continues to be a controversial
topic, but is an important factor in pharmacovigilance.
Without distinguishable nonproprietary naming, product
traceability can be degraded and safety signals can be attributed
to the wrong product and inappropriately deemed class
effects (e.g., effects found throughout the class of biologics).115
Distinguishable nonproprietary naming also increases the level
of accountability of the manufacturer.
WHAT TO EXPECT NEXT
Availability of biosimilars in the U.S. market brings with it the
need to monitor patient safety related to use of these new
products. With biosimilars, it is imperative that regulatory
and industry come together to create the most appropriate
pharmacovigilance and safety monitoring process, inclusive of
46
agreed-to naming guidance, to understand patient experience
and to be able to proactively, quickly, and accurately identify
potential safety signals across categories/medications. All
constituents participating in the healthcare system are vested
in the safe and appropriate use of biosimilars.
LOOKING AHEAD
47
LOOKING AHEAD
Our current healthcare system places a premium on value,
but this emphasis reflects more than just cost savings.
Equally important are innovation and competition in the
medical marketplace, which set the stage for development of
alternatives to currently available medications. Biosimilars are
uniquely poised to increase value in the healthcare system,
both now and in the future. The ultimate impact of biosimilars
will be driven by the answers to several key questions:
How will payers respond to the launch of biosimilars? Payer
responses are likely to evolve on several issues, such as
the relative speed in which formulary, coverage, and policy
decisions will be addressed after the initial launch of a biosimilar.
It also remains to be seen whether payers will take differing
approaches to biosimilars based on the structural complexity of
the compounds.72
How will employer purchasers influence uptake in the biosimilar
market? There will be a combination of factors that determine
uptake/utilization. Employers may not always follow national
formularies,78 because they are willing to pay more to have PBMs
administer a formulary that offers more choice to their employers
and families.116
Will biosimilar market uptake reflect factors beyond opportunity
for savings? Driving down costs of biologics is an ongoing
initiative across the healthcare market. However, without a track
record for U.S. market differentiation, it is unclear which key
features and benefits—aside from cost-savings projections—will
be most important in driving biosimilar uptake for particular
stakeholder categories. For example, each biosimilar will be
reviewed and approved on a case-by-case basis;9 which could
potentially be influenced by a range of factors such as indication
extrapolation, administration devices, and interchangeability
designation.1 In addition, each manufacturer of a biosimilar
may also influence market differentiation through experience,
reliability, and support services.80
48
as interchangeable.106 As one can assume, the outcome of this
debate will have wide impact, including to ePrescribing, EMRs,
claims systems, historical databases, drug inventories, inventory
management, and drug labels.
How will stakeholders value factors related to reimbursement?
CMS’ final rule provides that, for reimbursement purposes, all
biosimilars of a single reference product will be pooled within
the same HCPCS code on the basis of weighted average sales.22
This pooling methodology does not distinguish the relative value
of biosimilars with more or fewer approved indications.106 It is
also blind to the market experience of individual biosimilars, and
to market history of these biosimilars’ manufacturers.106
BIOSIMILARS
LANDSCAPE
Each stakeholder, in evaluating and acting upon these and many
other, future considerations, plays a critical role in developing a
long-term, sustainable market for biosimilars in the U.S.
UNCOVERING THE
UNKNOWNS
How will naming of biosimilars be determined, and what are
the ramifications? The process of naming a biosimilar is not as
straightforward as it may seem. For example, a distinguishable
nonproprietary name could potentially reduce the likelihood of
unintended switching or substitution, but might also negatively
impact the prescribing and dispensing of the biosimilar.106
There are also questions about whether the nonproprietary
names should be changed when manufacturers merge or when
products change hands, or when biosimilars are designated
INTRODUCTION
How will appropriate use in therapy evolve as various
stakeholders become more familiar with biosimilars? Biosimilars
are likely to gain increased acceptance over time.72 The increasing
influence of evidence-based practice guidelines on payer
coverage policy117 suggests that inclusion of biosimilars in such
guidelines will help stakeholders appreciate their appropriate
role in therapy. Physician and patient acceptance are important
for market uptake in the U.S.118
GAME CHANGERS
LOOKING AHEAD
49
GLOSSARY
50
ASP The average sales price (ASP) is a calculation of the
weighted average of manufacturer’s sales price for a drug for all
purchasers, net of price adjustments.119
Biosimilar A biological product that is highly similar to a U.S.licensed reference biological product notwithstanding minor
differences in clinically inactive components, and for which there
are no clinically meaningful differences between the biological
product and the reference product in terms of the safety, purity,
and potency of the product.9
CD20 Cluster of differentiation 20 (CD20) is a protein found on
B cells (a type of white blood cell). It may be found in higher
than normal amounts in patients with certain types of B-cell
lymphomas and leukemia.6
CDC The Centers for Disease Control and Prevention (CDC) is a
U.S. federal government agency whose mission is to protect public
health by preventing and controlling disease, injury, and disability.6
EGFR Epidermal growth factor receptor (EGFR) is a protein on
the surface of cells that binds with epidermal growth factor and
is therefore involved in cell division.6
EMA The European Medicines Agency (EMA) is a decentralized
agency of the EU that is responsible for the scientific evaluation
of medicines developed by pharmaceutical companies for use in
the EU.120
ESA Erythropoiesis-stimulating agent (ESA) is a substance that
stimulates the bone marrow to make more red blood cells.6
Extrapolation The process by which a proposed biosimilar
product may be licensed in one or more additional conditions
of use for which the reference product is licensed, if appropriate
scientific justification is provided and the patent landscape
allows for it. In practical terms, this means that the biosimilar
can receive approval for multiple indications without undergoing
clinical testing in those conditions as long as the reference
product itself was approved in those conditions.9
REFERENCES
Biologic A substance derived from a living organism or its
products that is used in the diagnosis, prevention, or treatment
of disease. Examples of biologic medicines include recombinant
proteins, allergy shots, vaccines, and hematopoietic growth factors.6
GLOSSARY
AE An adverse event (AE) is an unexpected medical occurrence
in a patient that happens during treatment with a drug or
other therapy.6
FDA The U.S. Food and Drug Administration (FDA) is an agency
in the U.S. federal government whose mission is to protect public
health by assuring the safety, efficacy, and security of human
and veterinary drugs, biological products, medical devices, the
nation’s food supply, cosmetics, and nutritional supplements.6
G-CSF Granulocyte-colony stimulating factor (G-CSF) is a
protein that stimulates bone marrow to produce granulocytes
and stem cells and release them into the bloodstream.6
Generic Medicine A prescription drug that has the same activeingredient formula as a brand-name drug. Generic drugs usually
cost less than brand-name drugs and are rated by the FDA to be
as safe and effective as brand-name drugs.121
HCPCS The Healthcare Common Procedure Coding System
(HCPCS) is a collection of standardized codes that represent
medical procedures, supplies, products, and services. The codes
are used to facilitate the processing of health insurance claims.121
HER2 Human epidermal growth factor receptor 2 (HER2) is a
protein involved in normal cell growth. It is found on some types
of cancer cells, including breast and ovarian.6
51
GLOSSARY
HGH Human growth hormone (HGH) is a hormone secreted
by the anterior pituitary gland that stimulates body growth
generally and the lengthening of long bones in particular.6
J-Code A subset of the most commonly used Healthcare
Common Procedure Coding System (HCPCS) Level II Codes
with a high-order value of “J” (See HCPCS).121
IDN Integrated Delivery Network (IDN) is a network of healthcare
organizations under a parent holding company.91
mAb A monoclonal antibody (mAb) is a type of protein made in
the laboratory that can bind to substances in the body, including
cancer cells.6
Interchangeability An “interchangeable” biological product
is biosimilar to the reference product and can be expected to
produce the same clinical result as the reference product in any
given patient. If administered more than once to an individual
(as many biological products are), the risk in terms of safety
or diminished efficacy of alternating or switching between use
of the biological product and the reference product will not be
greater than the risk of using the reference product without such
alternation or switch. A biosimilar should only be considered
interchangeable with the reference product if the FDA has
approved it as a biosimilar and designated it as interchangeable,
once additional criteria have been met.1
INN Allocated by the World Health Organization, an International
Nonproprietary Name (INN) identifies pharmaceutical
substances or active pharmaceutical ingredients. Each INN is a
unique name that is globally recognized and is public property.
A non-proprietary name is also known as a generic name.122
INF Interferon (INF) is a biological response modifier (a substance
that can improve the body’s natural response to infections and
other diseases). Interferons interfere with the division of cancer
cells and can slow tumor growth.6
52
PBM Pharmacy benefit manager (PBM) is most often a thirdparty organization that provides prescription drug programs
and services to help maximize drug effectiveness and contain
drug expenditures by influencing the behaviors of prescribing
physicians, pharmacists, and members. PBMs can be a service
inside of an integrated healthcare system (See IDN).123
P&T Committee A Pharmacy and Therapeutics Committee is an
advisory committee responsible for developing and maintaining
a formulary and establishing and implementing policies on the
use of drug products.124
Pharmacovigilance Procedures that monitor the safety of
medicines to detect, assess, understand, and prevent adverse
events or any other safety-related issues.122
Reference Product A reference product (aka, originator product)
is a previously licensed product used as the comparator for headto-head comparability studies with the similar biotherapeutic
product in order to show similarity in terms of quality, safety,
and efficacy. Is sometimes also referred to as the innovator
or originator product that the biosimilar product is intended
to copy.9
GLOSSARY
Switching A practice wherein a prescriber (or the prescriber’s
delegate, under direct supervision of the prescriber) may
change the prescription from one biologic medicine to another
biologic medicine.
REFERENCES
Substitution A practice allowed by law wherein a pharmacist
may dispense an alternative biologic medicine for a prescribed
biologic medicine without the prior approval of the prescriber.
In some U.S. states, there is ongoing dialogue regarding postdispensing notification and documentation. Private organization
management of substitution may vary based on formulary
decisions and other factors.
VEGF Vascular endothelial growth factor (VEGF) is a signal
protein produced by cells that stimulates vasculogenesis
and angiogenesis.6
WAC Wholesale acquisition cost (WAC) is an estimate of the
manufacturer’s list price for a drug to wholesalers or direct
purchasers, not including discounts or rebates.119
WHO The World Health Organization (WHO) is the directing
and coordinating authority for health within the United Nations
system. The WHO sets standards for disease control, health care,
and medicines; conducts education and research programs; and
publishes scientific papers and reports.125
53
REFERENCES
54
U.S. Food and Drug Administration. Information for Consumers
2.
product development. News Release. February 9, 2012.Available at: http://
DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm291232.
ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/
htm. Accessed on March 1, 2016.
release. July 24, 2014. Available at: http://www.sandoz-biosimilars.com/en/
U.S. oncologists in clinical practice. Cancer Medicine 2014; 3(4): 889–899
mediacenter/press_releases/140724_FDA_accepts_Sandoz_application_
Patient Protection and Affordable Care Act. December
for_biosimilar_filgrastim.shtml. Accessed on March 1, 2016.
6.
August 11, 2014.Available at: http://www.celltrion.com/en/company/notice_
March 1, 2016.
view.asp?idx=456&code=ennews&intNowPage=1&menu_num=&align_
Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann
year=all. Accessed on March 1, 2016.
Application for Pegfilgrastim. News release. December 17, 2014. Available
implications. GaBI Journal. 2012;1(1):13-6.
at: http://www.apotex.com/global/about/press/20141217.asp. Accessed on
National Cancer Institute. Dictionary of Cancer Terms. Available at: http://
U.S. Food and Drug Administration. Guidance for Industry: Biosimilars:
Additional Questions and Answers Regarding Implementation of the
Biologics Price Competition and Innovation Act of 2009. Draft Guidance.
May 2015. Available at: http://www.fda.gov/downloads/Drugs/.../
Guidances/UCM273001.pdf. Accessed on March 1, 2016.
8.
U.S. Food and Drug Administration. Drug Price Competition and Patent
Term Restoration Act of 1984 (Hatch-Waxman Amendments). August 2003.
Available at: http://www.fda.gov/NewsEvents/Testimony/ucm115033.htm.
Accessed on March 1, 2016.
9.
13. Apotex. Apotex Announces FDA Has Accepted For Filing its Biosimilar
Declerck, PJ. Biologicals and biosimilars: a review of the science and its
www.cancer.gov/publications/dictionaries. Accessed on March 1, 2016.
7.
12. Celltrion. Celltrion files for US FDA approval of Remsima. News Release.
GuidanceComplianceRegulatoryInformation/UCM216146.pdf. Accessed on
Oncol. 2008;19:411-419.
5.
Sandoz. FDA accepts Sandoz application for biosimilar filgrastim. News
Camacho LH, Frost CP, Abella E, et al. Biosimilars 101: considerations for
2009. Available at: http://www.fda.gov/downloads/Drugs/
4.
11.
U.S. Food and Drug Administration. Guidance for Industry: Scientific
Considerations in Demonstrating Biosimilarity to a Reference Product.
Final Guidance. April 2015. Available at: http://www.fda.gov/downloads/
DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM291128.
pdf. Accessed on March 1, 2016.
REFERENCES
3.
10. U.S. Food and Drug Administration. FDA issues draft guidance on biosimilar
(Biosimilars). August 2015. Available at: http://www.fda.gov/Drugs/
ucm241718.htm. Accessed March 1, 2016.
GLOSSARY
1.
March 1, 2016.
14. U.S. Food and Drug Administration. FDA approves first biosimilar product
Zarxio. News Release. March 6, 2015. Available at: http://www.fda.gov/
NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm. Accessed
on March 1, 2016.
15. Centers for Medicare and Medicaid Services. Food and Drug Administration
Approval of First Biosimilar Product. MLN Matters. Available at: https://
www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/
MLNMattersArticles/Downloads/SE1509.pdf. Accessed March 1, 2016.
16. Centers for Medicare and Medicaid Services. Medicaid Drug Rebate
Program Notice for Participating Drug Manufacturers. March 30, 2015.
Available at: http://www.medicaid.gov/Medicaid-CHIP-ProgramInformation/By-Topics/Benefits/Prescription-Drugs/Downloads/RxReleases/MFR-Releases/mfr-rel-092.pdf. Accessed March 1, 2016.
17. Centers for Medicare and Medicaid Services. Part D Requirements for
Biosimilar Follow-On Biological Products. March 30, 2015. Available at:
http://www.amcp.org/WorkArea/DownloadAsset.aspx?id=19358.
Accessed March 1, 2016.
55
REFERENCES
18. U.S. Food and Drug Administration. Guidances (Drugs)—Biosimilars.
24. Hospira. Hospira Submits New Biologics License Application to U.S. FDA
November 2015. Available at: http://www.fda.gov/Drugs/
for Proposed Epoetin Alfa Biosimilar. News Release. January 12, 2015.
GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm.
Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=175550&p=irol-
newsArticle&ID=2006860. Accessed March 1, 2016.
19. Centers for Medicare and Medicaid Services. Medicare Program; Revisions
to Payment Policies under the Physician Fee Schedule and Other Revisions
25. Apotex. Apotex Announces FDA Has Accepted For Filing its Biosimilar
Application for Filgrastim. News Release. February 17, 2015. Available at:
to Part B for CY 2016. Available at: https://www.cms.gov/Medicare/
http://www.apotex.com/global/about/press/20150217-2.asp. Accessed
Medicare-Fee-for-Service-Payment/PhysicianFeeSched/PFS-Federal-
March 1, 2016.
Regulation-Notices-Items/CMS-1631-P.html. Accessed March 1, 2016.
20. U.S. Food and Drug Administration. Guidance for Industry.
Nonproprietary Naming of Biological Products. Draft Guidance.
26. Amgen. Data on File. News Release. 25 November 2015.
27. Sandoz. FDA accepts Sandoz regulatory submission for a proposed
biosimilar etanercept. News Release. October 2, 2015. Available at: https://
August 2015. Available at: http://www.fda.gov/downloads/drugs/
www.novartis.com/news/media-releases/fda-accepts-sandoz-regulatory-
guidancecomplianceregulatoryinformation/guidances/ucm459987.pdf.
submission-proposed-biosimilar-etanercept. Accessed March 1, 2016.
21. Sandoz. Court ruling paves the way for launch of Sandoz’s Zarxio as first
U.S. biosimilar. News Release. July 22, 2015. Available at: http://www.sandoz.
com/media_center/press_releases_news/global_news/2015-07-22-courtruling-paves-the-way-for-launch-of-sandozs-zarxio-as-first-us-biosimilar.
shtml. Accessed March 1, 2016.
22. Centers for Medicare and Medicaid Services. Proposed policy, payment,
and quality provisions changes to the Medicare Physician Fee Schedule
for Calendar Year 2016. October 30, 2015. Available at: https://www.cms.
gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheetsitems/2015-10-30-2.html. Accessed March 1, 2016.
23. Slavitt A. MedPAC. File Code CMS-1631-P. Letter. September 8, 2016.
Available at: http://www.medpac.gov/documents/comment-letters/medpaccomment-on-cms’s-proposed-rule-on-the-physician-fee-schedule-andother-revisions-to-part-b.pdf?sfvrsn=0. Accessed April 5, 2016.
28. U.S. Food and Drug Administration. 2015-2016 Advisory Committee
Tentative Meetings. November 2015.Available at: http://www.fda.gov/
AdvisoryCommittees/ucm414515.htm. Accessed March 1, 2016.
29. Amgen. Data on File. 2016 Potential Approvals: Apotex. November 13, 2015.
30. Wang J, Chow SC. On the Regulatory Approval Pathway of Biosimilar
Products. Pharmaceuticals 2012, 5, 353-368.
31. European Medicines Agency. European public assessment reports. February
7, 2016. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/
medicines/landing/epar_search.jsp&mid=WC0b01ac058001d125. Accessed
on March 1, 2016.
32. GABI. Biosimilars approved in Australia. February 5, 2016. Available at:
http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-inAustralia. Accessed on March 1, 2016.
33. GABI. Biosimilars approved in Japan. February 19, 2016. Available at: http://
www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Japan.
56
44. Health and Human Services. 340B Drug Pricing Program Omnibus
2016. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/
Guidance. August 28, 2015. Available at: https://www.gpo.gov/fdsys/pkg/
drug-med/index-eng.php. Accessed on March 1, 2016.
FR-2015-08-28/pdf/2015-21246.pdf. Accessed March 1, 2016.
35. Dalgaard K. et al. Biosimilars seven years on: Where are we and what’s next.
45. Pharmaceutical Benefits Scheme. Letter to pharmacists - Biosimilar
infliximab on the PBS. 1 December 2015. Available at: http://www.pbs.gov.
media/mckinsey/dotcom/client_service/pharma%20and%20medical%20
au/info/publication/factsheets/biosimilars/letter-to-pharmacist-biosimilar-
products/pmp%20new/pdfs/biosimilars%20seven%20years%20on_
infliximab-on-the-pbs-2015-12. Accessed on February 7, 2016.
36. Long, D. Impact of Biosimilars on the Pharmaceutical Industry. September
46. Pharmaceutical Benefits Scheme. Biosimilar Medicines—Factsheet for
Healthcare Professionals. Available at: http://www.pbs.gov.au/publication/
2015. Presented at Magellan Rx Specialty Summit; September 1-3, 2015;
factsheets/biosimilars/biosimilars-factsheet-healthcare-professionals.pdf.
New York, NY.
Accessed on February 4, 2016.
37. IMS. Assessing biosimilar uptake and competition in European markets.
47. Canada Market Access Briefing. [White Paper] 2015. Available at: http://
October 2014. Available at: https://www.imshealth.com/files/web/
www.precisionadvisors.com/wp-content/uploads/2015/03/Canada-White-
IMSH%20Institute/Healthcare%20Briefs/Assessing_biosimilar_uptake_and_
Paper.pdf. Accessed on February 7, 2016.
competition_in_European_markets.pdf. Accessed on March 1, 2016.
38. Cber. World Economic League Table 2015 Highlights.December 26, 2014.
Available at: http://www.cebr.com/reports/world-economic-leaguetable-2015/. Accessed on March 1, 2016.
39. Bacharidis N. Tendering & Contracting for generic & branded medicines
across Europe—a comparison and benchmarking. Presented in November
2011; Birmingham, UK. Available at: http://www.ghp.org.uk/ContentFiles/
PDIG%20Nico%20Bacharidis%20Presentation%20-%20Nov%202011.pdf.
40. Neiderwieser D, Schmitz S. Biosimilar agents in oncology⁄haematology:
from approval to practice. Eur Jrnl Hematol. 2010. 277-288.
41. EuropaBio. EuropaBio’s Statement on French Substitution Policy. January
24, 2014. Available at: http://www.europabio.org/news/europabiosstatement-french-substitution-policy. Accessed on March 1, 2016.
42. GABI. Australian guidelines for biosimilars. August 7, 2015. Available at:
http://gabionline.net/Guidelines/Australian-guidelines-for-biosimilars.
43. Commonwealth of Australia. Economics Legislation Committee - National
Health Amendment (Pharmaceutical Benefits) Bill 2015 [Provisions].
June 2015.
REFERENCES
[White Paper] February 2013. Available at: http://www.mckinsey.com/~/
white%20paper.ashx. Accessed on March 1, 2016.
GLOSSARY
34. Health Canada. Summary Basis of Decision Documents: Drugs. February 4,
48. Health Canada. Interchangeability/Substitutability of Subsequent Entry
Biologics (SEBs). [Letter] July 29, 2010.
49. Zafar SY, Peppercorn JM, Schrag D, et al. The financial toxicity of cancer
treatment: a pilot study assessing out-of-pocket expenses and the insured
cancer patient’s experience. Oncologist 2013;18:381-90.
50. Rickwood S, Di Biase S. Searching for Terra Firma in the Biosimilars and
Non-Original Biologics Market. [White Paper] 2013.
51. Data on File, Amgen. IMS Health MIDAS 2014. August 20, 2015.
52. Data on File, Amgen. Comparison of Biosimilar Rules and Guidelines.
December 4, 2015.
53. U.S. Food and Drug Administration. News events: NDA, ANDA, IND & RDRC.
Available at: www.fda.gov/downloads/Drugs/NewsEvents/UCM245363.pdf.
Accessed on February 7, 2016.
54. European Medicines Agency. Guideline on Similar Biological Medicinal
Products. October 23, 2014. Available at: http://www.ema.europa.eu/docs/
en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf.
55. Kozlowski S. U.S. FDA Perspectives on Biosimilar Biologic Products. Presented
at: Biotechnology Technology Summit. June 13, 2014; Rockville, MD.
57
REFERENCES
56. National Conference of State Legislatures. State Laws and Legislation
Related to Biologic Medications and Substitution of Biosimilars. February
Managed Care Magazine. October 2010. Available at: http://www.
8, 2016. Available at: http://www.ncsl.org/research/health/state-laws-and-
managedcaremag.com/archives/2010/10/specialty-pharmacy-management-
legislation-related-to-biologic-medications-and-substitutionof-biosimilars.
will-become-more-intense. Accessed on March 1, 2016.
aspx. Accessed on March 1, 2016.
57. Neas RG, Gaugh DR. What’s in a name?—the identification of biologic
products. Journal of Generic Medicines: 2013 vol. 10 no. 3-4 148-158.
58. Casadevall N, Felix T, Strober B, Warnock D. Similar Names for Similar
Biologics. BioDrugs. 2014:Oct;28(5):439-44.
59. Grampp G, Ramanan S. The Diversity of Biosimilar Design and Development:
Implications for Policies and Stakeholders. BioDrugs. 2015 Nov 18.
60. U.S. Food and Drug Administration. Purple Book: Lists of Licensed
65. Milliman. Commercial Specialty Medication Research: 2016 Benchmark
Projections. Research Report. 28 December 2015. Available at: http://
us.milliman.com/uploadedFiles/insight/2016/commercial-specialtymedication-research.pdf. Accessed on March 1, 2016.
66. Artemetrx. Specialty Drug Management. 22 April 2015. Available at: http://
businesshealthcaregroup.org/wp-content/uploads/2009/11/WisconsinExternal-Slides-April-2015-FINAL.pdf. Accessed on March 1, 2016..
67. UnitedHealth Center for Health Reform & Modernization. The Growth of
Biological Products with Reference Product Exclusivity and
Specialty Pharmacy: Current trends and future opportunities. Issue Brief.
Biosimilarity or Interchangeability Evaluations. 3 September 2015.
April 2014. Available at: http://www.unitedhealthgroup.com/~/media/uhg/
Available at: http://www.fda.gov/drugs/developmentapprovalprocess/
pdf/2014/unh-the-growth-of-specialty-pharmacy.ashx. Accessed on
howdrugsaredevelopedandapproved/approvalapplications/
March 1, 2016.
therapeuticbiologicapplications/biosimilars/ucm411418.htm. Accessed on
February 7, 2016.
61. Olson K. Biosimilar naming and labeling: a study of U.S. pharmacists.
68. Stern D, Reissman, D. Specialty Pharmacy Cost Management Strategies of
Private Health Care Payers. J Manag Care Pharm. 2006;12(9):736-44
69. Olson K. ASBM Labeling Survey. February 2015. ISR Report. Available at:
October 2015. Available at: http://docs.house.gov/meetings/IF/
http://docs.house.gov/meetings/IF/IF14/20160204/104408/HHRG-114-IF14-
IF14/20160204/104408/HHRG-114-IF14-20160204-SD009.pdf. Accessed
20160204-SD010.pdf. Accessed on March 1, 2016.
March 1, 2016.
62. Centers for Medicare & Medicaid Services. CMS Finalizes Hospital
Outpatient and Ambulatory Surgical Center Policy and Payment Changes,
Including Changes to the Two-Midnight Rule and Quality Reporting for 2016.
October 30, 2015.
63. Mulcahy AW, Predmore Z and Mattke S. The Cost Savings Potential
of Biosimilar Drugs in the United States. Santa Monica, CA: RAND
Corporation, 2014.
58
64. Collins S. Specialty Pharmacy Management Will Become More Intense.
70. Amgen, Data on File. IMS Health National Sales Perspective (NSP) Audit
October 29 2015.
71. Amgen, Data on File. 2015 Biosimilars Roundtable Advisory Board.
September 26, 2015. Dallas, TX.
72. Ventola CS. Evaluation of Biosimilars for Formulary Inclusion - Factors for
Consideration by P&T Committees. P T. 2015 Oct; 40(10) 680–689
to employers. December 2011. Available at: http://us.milliman.com/
uploadedFiles/insight/health-published/understanding-biosimilars.pdf.
74. Centers for Medicare and Medicaid Services. How Medicare Prescription
Drug Plans & Medicare Advantage Plans with Prescription Drug Coverage
83. Minutolo R, Borzumati M, Sposini S, et al. Am J Kidney Dis. 2016. Feb 13.
84. Global Healthy Living Foundation. Patient Perspectives on Medication
Switching for Non-Medical Reasons: A survey of stabilized patients by
the Global Health Living Foundation. April 23, 2015. Available at: http://
www.50statenetwork.org/wp-content/uploads/2015/04/GHLF-SwitchingStable-Patients-Survey_Summary.pdf. Accessed on March 1, 2016.
85. Floodmark et al; Switching from originator to biosimilar human growth
October 2015. Available at: https://www.medicare.gov/Pubs/pdf/11136.pdf.
hormone using dialogue teamwork: single-center experience from Sweden.
Accessed: March 1, 2016.
Biol Ther (2013) 3: 35-43.
75. ExpressScripts. Plan Design Review Guide. December 2010. Available at:
86. Panaccione R, Ghosh S. Optimal use of biologics in the management of
https://www.express-scripts.com/art/corporate/pdf/plan_design_review_
Crohn’s disease. Therapeutic Advances in Gastroenterology. 2010;3(3):179-
guide.pdf. Accessed on March 1, 2016.
189.
76. Academy of Managed Care Pharmacy. Specialty Pharmacy and Biosimilars.
87. U.S. Food and Drug Administration Voice Blog. FDA Offers Free, Continuing
[Presentation] February 2015. Available at: http://www.amcp.org/
Education Course to Help Health Care Providers Understand ‘Biosimilars’.
WorkArea/DownloadAsset.aspx?id=19133. Accessed on March 1, 2016.
February 18, 2016. Available at: http://blogs.fda.gov/fdavoice/index.
77. Avalere. Value Based Formulary Design: Is Premera A Voice Crying
in the Wilderness? Presented at ISPOR Annual Meeting; May 1620, 2015; Philadelphia. Available at: http://www.ispor.org/Event/
GetReleasedPresentation/327. Accessed on March 1, 2016.
78. Teton County Navitus. PHARMACY BENEFIT MANAGEMENT SERVICES
AGREEMENT (10202015). January 1, 2016. Available at: http://www.tetonwyo.
php/2016/02/fda-offers-free-continuing-education-course-to-help-healthcare-providers-understand-biosimilars/. Accessed on March 1, 2016.
88. Sandoz. ZARXIO™ (filgrastim-sndz). [Prescribing Information] March
2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/
label/2015/125553lbl.pdf. Accessed on March 1, 2016.
89. Academy of Managed Care Pharmacy (AMCP). AMCP Format for Formulary
org/cc/docs/StaffReports/2015-BCC/10-20/1020-15-NavitusContract.pdf.
Submissions. 2015. Available at: http://www.amcp.org/Tertiary.aspx?id=8435.
79. Fitch Ratings. 2015 Outlook: U.S. Nonprofit Hospitals and Healthcare
90. Medicare Payment Advisory Commission (MedPAC). Overview of the 340B
Systems. December 9, 2014. Available at: http://www.calhospital.org/sites/
Drug Pricing Program, May 2015. Available at: http://www.medpac.gov/
main/files/file-attachments/fitch_2015_healthcare_outlook.pdf. Accessed
documents/reports/may-2015-report-to-the-congress-overview-of-the-
on March 1, 2016.
340b-drug-pricing-program.pdf?sfvrsn=0. Accessed on March 1, 2016.
80. Griffith N, McBride A, Stevenson JG, Green L. Formulary Selection Criteria
for Biosimilars Considerations for US Health-System Pharmacists. Hospital
Pharmacy. 2014;49(9) 813-825.
81. Jacobs IA, Singh E, Swell KL et al. Patient Understanding and Attitudes
REFERENCES
(MA-PDs) Use Pharmacies, Formularies, & Common Coverage Rules.
GLOSSARY
73. Milliman. Understanding biosimilars and projecting the cost savings
91. The Advisory Board Company. Post-Acute Care Cheat Sheet: Integrated
Delivery Networks. Available at: https://www.advisory.com/research/postacute-care-collaborative/members/resources/cheat-sheets/integrateddelivery-networks. Accessed on March 1, 2016.
About Biosimilars: An International Cross-Sectional Survey. Value in Health.
2015 (18) A335 – A766.
82. QuantiaMD. Reading the Signs: A Roadmap for Engaging Physicians in the
Biosimilars Discussion. Web-based survey. March 2016.
59
REFERENCES
92. Health Resources and Services Administration. 42 CFR Part 10: 340B Drug
Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties
April 16, 2014. Available at: http://www.businesswire.com/news/
Regulation. June 17, 2015. Available at: https://www.gpo.gov/fdsys/pkg/FR-
home/20140416005356/en/Epirus-Zalicus-Announce-Merger-Agreement.
2015-06-17/pdf/2015-14648.pdf. Accessed March 1, 2016.
93. 340B Health Organization. About. Available at: http://www.340bhealth.org/
about. Accessed on January 3, 2016. Accessed on March 1, 2016.
94. Government Accountability Office. Medicare Part B Drugs. Report to
102.Amgen. Amgen and Watson Announce Collaboration to Develop and
Commercialize Oncology Biosimilars. News Release. December 19, 2011.
Available at: http://www.prnewswire.com/news-releases/amgen-and-
Congressional Requesters. June 2015. Available at: http://gao.gov/
watson-announce-collaboration-to-develop-and-commercialize-oncology-
assets/680/670676.pdf. Accessed on March 1, 2016.
biosimilars-135880803.html. Accessed on March 1, 2016.
95. National Association of Community Health Centers (NACHC).
103.Johnson SJ. Pfizer-Allergan deal could reduce biosimilar cost savings.
Understanding the 340B Program: A primer for health centers. May 2011.
Modern Healthcare. December 5, 2015. http://www.modernhealthcare.com/
Available at: http://www.nachc.org/client/documents/5.11%20340%20
article/20151205/MAGAZINE/312059970?template=print. Accessed on
Manual%20Primer%20for%20Health%20Centers1.pdf. Accessed on March 1,
March 1, 2016.
2016.
96. ASHP Expert Panel on Drug Product Shortages. ASHP Guidelines on
104.Schmidt R, Suzuki S, Neuman K. Medicare Drug Spending. 11 September
2015. Available at: http://www.medpac.gov/documents/september-2015-
Managing Drug Product Shortages in Hospitals and Health Systems. Am J
meeting-presentation-medicare-drug-spending.pdf?sfvrsn=0. Accessed on
Health Syst Pharm. 2009 Aug 1;66(15):1399-406 at 1399
March 1, 2016.
97. Becker DJ, Talwar S, Levy BP, et al. Impact of Oncology Drug Shortages
on Patient Therapy: Unplanned Treatment Changes. Journal of Oncology
Practice. 2013;9(4):e122-e128 at e125-6
98. Government Accountability Office. Drug Shortages: Public Health Threat
Continues, Despite Efforts to Help Ensure Product Availability. February
105.Centers for Medicare and Medicaid Services. Medicare Program; Part B Drug
Payment Model. March 8, 2016. Available at: https://s3.amazonaws.com/
public-inspection.federalregister.gov/2016-05459.pdf. Accessed on March
10, 2016.
106.House of Representatives Subcommittee on Health Committee on
2014. Available at: http://www.gao.gov/assets/670/660785.pdf. Accessed
Energy and Commerce. Examining Implementation of the Biologics
on March 1, 2016.
Price Competition and Innovation Act. [Transcript] February 4, 2016;
99. Yurukoglu, Liebman and Ridley. The role of government reimbursement in
drug shortages. Nat. Bur. Econ.Res. 2016.
100.Pfizer. Pfizer Completes Acquisition of Hospira. News Release. September 3,
2015. Available at: http://www.pfizer.com/news/press-release/press-releasedetail/pfizer_completes_acquisition_of_hospira. Accessed on March 1, 2016.
60
101. Epirus. Epirus and Zalicus Announce Merger Agreement. News Release.
Washington, D.C. Available at: http://docs.house.gov/meetings/IF/
IF14/20160204/104408/HHRG-114-IF14-Transcript-20160204.pdf. Accessed
on March 1, 2016.
Benefit Manual: Chapter 6 – Part D Drugs and Formulary Requirements.
Available at: https://www.cms.gov/Medicare/Prescription-Drug-Coverage/
119. Mattingly J. Understanding Drug Pricing. US Pharm. 2012;37(6)(Generic
Drug Review suppl):4045.
120.European Medicines Agency. About Us. Available at: http://www.ema.
PrescriptionDrugCovContra/Downloads/Chapter6.pdf. Accessed on
europa.eu/ema/index.jsp%3Fcurl=pages/about_us/general/general_
January 19, 2016
content_000235.jsp%26mid=. Accessed on March 1, 2016.
108.Kopenski F. Understanding biosimilars and projecting the cost savings
uploadedFiles/insight/health-published/understanding-biosimilars.pdf.
109. Medicare Rights. Closing the Doughnut Hole. January 1, 2014. Available at:
https://www.medicare.gov/Pubs/pdf/11493.pdf. Accessed on March 1, 2015.
110. Lucio SD, Stevenson JG, Hoffman JM. Biosimilars Primer for the HealthSystem Pharmacist. Am J Health Syst Pharm. 2013;70(22)2004-2017.
111. Schellekens H. Biosimilar therapeutics-what do we need to consider? NDT
Plus. 2009;2(Suppl_1):i27-i36.
112. Zuñiga L, Calvo B. Biosimilars: pharmacovigilance and risk management.
Pharmacoepidemiol Drug Saf. 2010 Jul;19(7):661-9 at 663
121. Centers for Medicaid and Medicare Services. Glossary. Available at: https://
www.cms.gov/apps/glossary/. Accessed on March 1, 2016.
REFERENCES
to employers. December 2011. Available at: http://us.milliman.com/
GLOSSARY
107. Centers for Medicare and Medicaid Services. Medicare Prescription Drug
122. World Health Organization. Essential medicines and health products: Terms.
Available at: http://www.who.int/medicines/services/inn/en/ Accessed on
March 1, 2015.
123. Kingery. The Basics of Pharmacy Benefits Management. Anthem Virginia
CE Forum. 2009. Available at: https://www.anthem.com/shared/va/f5/s1/t0/
pw_b135247.pdf?refer=ahpagent&state=va. Accessed on March 14, 2016.
124.Tyler LS. ASHP Guidelines on the Pharmacy and Therapeutics Committee
and the Formulary System. Am J Health-Syst Pharm. 2008; 65:1272-83
125. World Health Organization. About Who. Available at: http://www.who.int/
about/en/. Accessed on March 1, 2016.
113. Grampp G, Machaon B, Felix T, et al. Active and passive surveillance of
enoxaparin generics: a case study relevant to biosimilars. Expert Opin Biol
Ther. 2014;14(3):1-12.
114. Liu M, McPeek Hinz ER, Matheny ME, et al. Comparative analysis of
pharmacovigilance methods in the detection of adverse drug reactions
using electronic medical records. JAMIA. 2013;20(3):420-426.
115. Casadevall N, Edwards R, Felix T, et al. Pharmacovigilance and biosimilars:
considerations, needs and challenges Expert Opin Biol Ther. 2013(13):10391047.
116. Miller S. Restrictive Formularies and Drug Exclusions: In Whose Interest?
November 20, 2014. Available at: https://www.shrm.org/hrdisciplines/
benefits/articles/pages/drug-formularies-exclusions.aspx. accessed on
March 1, 2016.
117. McCauley JL. Guidelines and Value-Based Decision Making: An Evolving
Role for Payers. N C Med J. 2015;76(4):243-246.
118. European Commission (EC). Pharmaceutical Industry: A strategic sector for
the European Economy. November 2014.
61
KEY QUESTIONS TO CONSIDER WHEN EVALUATING BIOSIMILARS
With the evolution of the biosimilar marketplace and remaining unknowns, there are still many considerations that have short and
long-term implications for building a sustainable market for biosimilars in the U.S. Below is a foundation of key elements to help
guide you as you consider the appropriate utilization of a biosimilar for you and your organization:
HOW WILL…
…an interchangeability designation, or lack thereof, impact decisions made around biosimilars?
…formulary decision makers manage biosimilars?
…patient and provider understanding of biosimilars impact uptake?
…contracting change as more biosimilars are introduced?
…biosimilar utilization pose challenges to existing information technology systems and processes?
…reimbursement change as more biosimilars enter the marketplace?
…the naming process impact the prescribing and dispensing of biosimilars?
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799
www.amgen.com
1
© 2016 Amgen. All rights reserved.
USA-BIO-122466(1)

- Biosimilars

Transcription

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