Five Strategic Considerations for Biosimilar
Commercialization By Rohit Sood, Sebastien Morisot, and Rafal Kokolus
With a large number of blockbuster biologics such as Erbitux
[cetuximab;
ImClone,
BMS]
and
Herceptin
[trastuzumab;
Genentech] expected to go offpatent in the next 5 years, the
global biosimilar market is expected to reach $15 billion by 2020.
More than 150 manufacturers are
currently investing in biosimilar development, manufacturing,
and commercialization capabilities across several key markets,
including South Korea, India,
China, Argentina, and in the
European Union (EU). Meanwhile,
advancements in technology and
capabilities as well as economic
necessities driving the need for less
expensive medicines have created
an opportunity for biosimilars in
the marketplace.
Biosimilar commercialization is
essentially similar to commercializing a biologic, but with two key
differences: the level and mix of
the investment and the commercial model. Through our research
and experience working with a
wide range of commercial organizations in the biotechnology
space, Campbell Alliance has identified five factors companies may
consider as they think about commercializing biosimilars: country,
category, company, competition,
and customer.
Country
In determining the countries in
which a product will be marketed, consideration must be given to
different levels of IP protection,
regulatory pathways, and policies
on interchangeability/ automatic
substitution.
Figure 1a: Go-to-market considerations should include IP and local market healthcare policies
Law against
automatic substitution
Guidelines prohibit
automatic substitution
Automatic substitution occuring;
No regulation/law
Sweden
Finland
NoMA encouraging
interchangeability
study for
REMSIMA
and REMICADE
Norway
Estonia
Latvia
Denmark
Lithuania
Ireland
UK
Netherlands
Belgium
Jan, 2014:
Law change
to allow automatic
substitution
for treatment
naiive patients
France
Belarus
Poland
Germany
Czech
Republic
Switzerland
Italy
Austria
Ukraine
Slovakia
Moldova
Hungary
Romania
Slovenia
Croatia
Serbia
Bulgaria
Cyprus
Spain
Portugal
Greece
Malta
Source: Campbell Alliance Insights
OBR; Published October 15, 2014;
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In Europe, biosimilar products
for growth have been available
for almost a decade. To push
back, manufacturers of originator drugs are using changes in
manufacturing procedures and for-
mulations to create new patent
protections. As they begin to invest
in the development of new biosimilars, manufacturers may consider
engaging outside council to conduct a patent mapping exercise to
Meanwhile,
policies
around
interchangeability and automatic substitution differ by region
(Figure 1a and 1b). In the EU, decisions regarding interchangeability
are decided by the individual countries. Due to concerns around the
traceability of adverse events,
almost all EU country regulatory bodies have established rules
against automatic substitution.1
However, there is some change on
the horizon.
Figure 1b: Markets with similar automatic substitution policies may result in varying
uptake given physician behavior and dynamics
1.4
Volume
Standard Units (millions)
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Q1
1998
Q1
2000
Q1
2002
0.7
Q1
2004
Q1
2006
Q1
2008
Q4
2009
Q1
2006
Q1
2008
Q4
2009
Volume
Standard Units (millions)
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Q1
1998
Q1
2000
Q1
2002
Q1
2004
Total of All Brands
First Generation Brands
Source: Campbell Alliance Insights
make sure that there is a development path with minimal barriers.
IP mapping is vital for addressing
not just the known IP implications
of a product but also the potential
unknown issues.
Second Generation Brands
Biosimilars
In January, France became the
first country to allow pharmacists
to substitute a biosimilar for a “reference biologic.” In Germany, a
large proportion of erythropoietin
is apparently being purchased by
dialysis clinics through a physician
organization equivalent to a group
purchasing organization, so physicians there appear to have direct
financial incentive to use the less
expensive product. In fact, German
physicians run the risk of being
held accountable for exceeding target cost limits in prescribing, which
is driving uptake for biosimilars.
Italy, Spain, and the UK have established guidance and official lists of
non-substitutable medicines that
include all biologics.
Here, in the US, legislation
regarding biosimilars varies from
state to state and is constantly evolving. Virginia, Utah, and
North Dakota have passed laws
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that permit pharmacists to dispense a biosimilar in place of a
prescribed biological product only
if that biosimilar meets the higher
safety standards for interchangeability. Meanwhile, states like
Arizona, Maryland, Mississippi,
and Washington have rejected similar laws. Numerous other states
have legislation that is expected to
be considered.
Category
Biosimilars are a relatively new
and evolving category with several
moving parts, including regulatory
pathways and substitution policies.
An opportunity exists to weave a
cohesive communication story to
raise awareness on biosimilars and
set expectations on the value of the
category to patients and the healthcare system.
The Medical Affairs organization
and medical science liaisons (MSLs)
have an important role to play in
raising market awareness of a biosimilar product. The C-suite will
also need to get involved in establishing credibility of a product and
the supply by participating in conferences and congresses to talk
about the assets and the level of
investment a company is making in
the category.
The value proposition of a biosimilar product will be a less
important consideration because it
should mirror the reference product. However, it will be necessary to
articulate what a company is bringing to the table aside from just the
lower cost in order to appeal to the
full range of stakeholders. Cost
will be important to payers, but
physicians and patients will also
be interested in efficacy and safety data and the support services
offered. Because these products
are not the equivalent of generics, a constant relationship and
maintenance will be necessary
after launch to make sure potential adverse events are monitored
(similar to branded products) and
physicians and patients are getting
the hand holding they need.
Company
Manufacturer
commitment,
credibility, and corporate equity
are critical for biosimilar acceptance. Based on research done by
Campbell Alliance, stakeholders’
familiarity with a manufacturer
has a major influence on the decision whether to prescribe the
product or not. In a survey of prescribers, a rheumatologist in France
noted, “If I know the company and
it’s what they do, of course I would
be more comfortable.” An oncologist in the US expressed that, “It
would give me peace of mind if the
product is coming from a big player
like Amgen or Genentech.”
Without the benefit of experience with a manufacturer,
prescribers and payers will want to
see information that helps them
understand why they should use
a product from this company. If a
manufacturer were able to demonstrate repeated success with
producing biosimilars as effective
and safe as originators, this would
be a trusted standard.
Competition
A significant number of competitors are interested in capitalizing
on the opportunity with biosimilars. Separation exists between
niche players and big pharma.
Mapping and addressing originator messaging and policy initiatives
will be critical.
The competition for biosimilar manufacturers is not
limited to originator products or
other biosimilars targeting the
same pathways. Biosimilar manufacturers must be keenly attuned
to the availability or ongoing development
of
second-generation
biologics that could compete directly against them. Second-generation
biologics are part of the lifecycle
management armamentarium for
biotechnology companies, and they
build upon the demonstrated track
record of an available molecule, by
improving its efficacy and safety
(e.g., Roche’s Kadcyla is an antibody
drug conjugate evolution of the
blockbuster Herceptin).
The ability of a second-generation manufacturer to shift the
standard of care paradigm and
convert patients from the original to the improved molecule will
significantly limit the need for a
biosimilar mimicking the original product. As a result, the market
potential for a biosimilar manufacturer facing this situation will
be restricted to a subset of a larger
space dominated by a second-generation product. Conversely, lack
of successful conversion from an
originator product to a secondgeneration product will create
opportunities for biosimilar manu-
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facturers to drive utilization, gain
market share from their originator competitor(s), and establish a
strong presence in their space.
When developing a biosimilar
of an originator product that utilizes a device, such as a pre-filled
syringe, biosimilar manufacturers
will be challenged to develop their
own device to match. Device design
and development requires very different capabilities and skill sets,
and biosimilar manufacturers that
are considering developing their
own devices need to have those
capabilities in house.
It will also be necessary to get
the device approved by the regulatory authorities. In the US, FDA
mandates the 510(k) regulatory pathway for the approval of any
new device. In the EU, meanwhile,
medical devices need to comply
with the appropriate legislative
directive, depending on the type of
device it is.
Customers
Finally, the customer landscape
is a complex mosaic involving physicians, payers, regulators, and
advocacy groups. These camps
have mixed views on biosimilars in
general.
Stakeholders
have
numerous questions relative to quality,
reliability, and confidence in biosimilars. Issues like indication
extrapolation are a concern when
a biosimilar of a drug with multiple indications has not been tested
in the full range of indications.
Gastroenterologists in the US and
Europe, for example, have stated
that they will not prescribe biosimilar infliximab in Crohn’s disease or
in patients with ulcerative colitis if
clinical trials have only been conducted in rheumatoid arthritis.2
Based on research conducted by
Campbell Alliance, prescribers are
interested in biosimilars. Among
a group of surveyed prescribers,
a general practitioner in the UK
expressed, “I have no real experience with biosimilars yet, but I’m
interested. Real cost savings. I’m
broadly positive.” Similarly, a general practitioner in Germany noted,
“Insurance will try to make it popular to prescribe biosimilars like
they do with generics, which is
okay.”
Less positively, a surveyed oncologist in the UK wondered, “If you
can’t replicate [the originator drug]
100%, then how can you get [the
biosimilar] to perform 100%?” A
US oncologist echoed a similar concern, asking, “Are they really as
good?”
To overcome stakeholder skepticism around biosimilarity, it
will be necessary to obtain advocacy for the product, educating
opinion leaders to alleviate confusion around product nomenclature,
and providing medical education
around the product attributes and
how it compares with the reference
drug.
Appealing to payers is the first
hurdle, because without assurance of reimbursement, physicians
will be reluctant to prescribe.
Payers acknowledge that biosimilars are comparable with their
biologic counterparts but not
necessarily equivalent, thereby
warranting a close inspection of
the biosimilar’s clinical, comparative, and market data (if available)
to determine appropriateness. In
addition, payers acknowledge that a
biosimilar could be chemically different but functionally the same
as the biologic, leading to several unknowns regarding “tolerable
variance.”
Another
important
aspect
of development in the biosimilar market is physician comfort
with the idea of prescribing the
agent. Ultimately, a physician’s
decision to sit with a patient to
discuss the option of using a biosimilar will vary by therapeutic
area, specialty, and the patient
dynamic. Physicians may be more
willing to start a new patient on
a biosimilar versus switching a
patient from a reference drug to a
biosimilar. Physicians tend to have
strong preferences for which treatments they use for which patients.
Unless they truly understand the
clinical and economic implications
of biosimilars, they will most likely
limit their use of biosimilars with
patients. And of course, they will be
limited by the automatic substitution policy in place.
A certain level of patient education may also be necessary. Patients
may be reluctant to switch to a different product that does not offer
the same quality of patient support—such as patient assistance
programs for specialized products—and they may not be fully
aware of biosimilars that have
not been on the market as long
as branded referenced products.
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On the other hand, patients will
value products with an efficacy similar (or better than) that of
their current treatment, with no
added side effects. Most importantly, out-of-pocket payments for both
non-insured and insured patients
will likely be reduced if switching
to a biosimilar-based treatment.
Conclusion
Despite the challenges, biosimilars can be an attractive
opportunity for companies looking to enter a therapeutic area or
for existing players looking to bolster their current position. Because
biosimilar development leverages
the scientific evidence established
by the reference product, initial
development steps involving target
identification and validation are
eliminated, decreasing the risk of
failures and the development time.
Provided that manufacturers can
demonstrate comparability, biosimilars can be developed with less
time, investment, and risks than is
associated with standard biologic
development pathways.
About the Contributors
Rohit Sood is Head of Global
Launch
Excellence,
Campbell
Alliance. He can be reached at
r s o o d @ c a mp b e l l a l l i a n c e. c o m .
Sebastien Morisot is Engagement
Manager, Campbell Alliance. He
can be reached at [email protected]. Rafal Kokolus
is Senior Engagement Manager,
Campbell Alliance. He can be
reached at [email protected].
Article References:
1.
2.
http://www.eahp.eu/page/biosimilars-do-not-look-mirror.
Accessed 8/12/14.
http://bio-trends.com/News-and-Events/Press-Releases/
TNF-alpha-inhibitors-093013. Accessed 8/12/14
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