Biosimilar interchangeability with reference
biologics remains a challenge years after product launches, with use depending
on physician comfort, experts said. Despite multiple state legislations
promoting biosimilar substitution, barriers to uptake remain as use is limited
to FDA-approved interchangeable biosimilars, of which there are currently none,
they noted.
Lack of interchangeability data and regulatory
guidance on using biosimilars in place of originators is a significant barrier
to biosimilar uptake. Furthermore, physician and patient education will likely
be a growing challenge as more oncology biosimilars get launched. Even though
one supportive care oncology biosimilar -- Zarxio (filgrastim-snz) by Novartis’
(VTX:NOVN) generics division Sandoz -- was approved in April 2015, upcoming
biosimilars used as treatment may face a higher uptake barrier.
A recent Medicare Part B policy change allows
for biosimilars to get an individual billing code under the Healthcare Common
Procedure Coding System (HCPCS) for reimbursement, which analysts have said
would encourage uptake and price competition. While experts agreed this will
help promote prescribing, they were more tempered in the policy having a major
and immediate impact on biosimilar usage, this news service reported on 27
February.
Lack of
interchangeability remains a barrier
The use of biosimilars is still dependent on
physician preference, said Michael Hunter, pharmacy management consultant,
Milliman, Chicago, Illinois. However, guidance on interchangeability, like
clinical evidence or data, would ultimately help the choice for biosimilars
over brands, which is still lacking, he added.
Analysts noted that Medicare considered
comments from various stakeholders during the comment period before the policy
was implemented. The comments showed that grouping biosimilars together led to
the impression that the products could be interchangeable. Even though
biosimilars may be approved for fewer indications than the reference product or
another biosimilar, the grouping could lead to misconceptions on
interchangeability without any evidence, analysts added.
The Medicare reimbursement policy change will
allow biosimilars to differentiate themselves from each other, which is appropriate
for products that are not medically interchangeable, said Richard Manning,
partner, Bates White Consulting, Washington DC.
However, experts said interchangeability --
where the biosimilars could be used in place of the reference biologics -- inherently
remains a challenge for biosimilar uptake. Despite biosimilars being grouped
together under one code in the past, they have largely not been
interchangeable, the noted.
Interchangeability is not done at the
pharmacist level as a physician’s approval is still required for biosimilar
use, said Dr Nabhan Chadi, vice president and chief medical officer, Cardinal
Health Specialty Solutions, Waukegan, Illinois, adding that at larger
institutions, these decisions are made by institutional committees. Physicians
have to specifically prescribe the biosimilar, said Hunter, adding that
interchangeability remains easier with small molecules and generics, which can
be done by a pharmacist. It is difficult to estimate the impact of this recent
reimbursement policy change when the long-term interchangeability guidance is
not known, said Hunter.
This news service has previously reported on
physician reservations on biosimilar interchangeability, particularly
interchangeability of biosimilars of AbbVie’s (NYSE:ABBV) Humira (adalimumab).
Amgen’s (NASDAQ:AMGN) Amjevita and Boehringer Ingelheim’s Cyltezo are both
approved but not launched. This news service reported 27 February that Amgen
would not be conducting interchangeability studies. Coherus Biosciences’
(NASDAQ:CHRS) CHS-1420 is in late-stage development, and recently had Phase III
equivalency data to Humira announced in August 2017.
Over the last five years, 37 states and Puerto
Rico allow biosimilar substitution to be covered under insurance, but it is not
clear if that has impacted uptake, said Chadi. While this promotes biosimilar
use, other barriers remain, he added. Most states that have enacted legislation
on biosimilar substitution require that the prescribing physician be notified
or be consulted in some manner about a substitution, said Manning.
It is important to note that while most state
laws allow substitution, they do so only of FDA recognized interchangeable
products, he noted. No biosimilars have that designation to date and getting
interchangeability on the label seems an unlikely reality in the near term, he
added. Until there is more experience with implementing the law in cases with
interchangeable biosimilars, it is very hard to say what type of substitutions
will be done, he added.
Biosimilar usage will be driven by the
collective expertise of the physician and pharmacist, said Steven Lucio,
associate vice president, Center for Pharmacy Practice Excellence, Vizient,
Irving, Texas. But there is a lack of a reliable source to give guidance on
interchangeability of biosimilars to pharmacists, said Suchira Ghosh, Counsel,
Axinn, Veltrop & Harkrider, New York.
Unlike the Orange book -- which is used by
pharmacists to make substitution decisions for generics -- the Purple book for
biologics and biosimilars does not give adequate information on whether
interchangeability is possible, and the decision is left to the clinicians or
state, she added. Guidelines by ASCO or NCCN do suggest biosimilar use, but
they could add more clarity on substitution to encourage use, said Chadi.
In larger institutions, the use of the
biosimilar in place of the originator drug is heavily driven by the payer
committees, and some payers have stuck with originator products despite the
availability of biosimilars he added.
Oncology uptake
faces larger barriers
Favorable reimbursement policies involving
separate billing codes such that continued development and therapeutic
competition is encouraged are especially important in oncology compared to
other conditions like rheumatoid arthritis, said Manning. However, oncologists
still need to become more familiar with biosimilars and there is a push for
education initiatives aimed at detailing the approval review rigor that
biosimilars undergo, said Lucio.
Physician education will be important
especially in the next few years as biosimilars for drugs like Roche’s
(VTX:ROG) Herceptin (trastuzumab) and Avastin (bevacizumab), used directly in
treatment, are launched, Lucio noted. There haven’t been any major reservations
with using Zarxio, a biosimilar for Amgen’s Neupogen (filgrastim), for treating
neutropenia, mainly because it is supportive care, said Chadi.
Zarxio has a clear surrogate marker of white
blood cell counts to indicate its efficacy in supportive care, but there aren’t
any similar markers for the Herceptin and Avastin biosimilars, said Lucio. Oncologists
would thus have to wait a long time to see if the biosimilar is working, he
noted. Mylan’s (NASDAQ:MYL) Ogivri, a biosimilar Herceptin and Amgen’s Mvasi, a
biosimilar for Avastin, were both approved in 2H17 but have not yet been
launched.
Patient education is also essential with the
use of biosimilars like Zarxio, since patients need explanations of why they
are being given a biosimilar substitution of branded product like Neupogen, how
the biosimilar has proven safety and efficacy and the rigor of the approval
process, said Sandeep Parsad, assistant director of Pharmacy, Cancer and
Investigational Drug Services at University of Chicago Medicine. There may be
instances where patients would be prescribed the originator, but their
insurance only covers the biosimilar, she explained.
Manasi Vaidya
Reporter, New York
Manasi Vaidya has a master’s degree
in biotechnology. After a stint in a research lab, she spent two years as
correspondent in India for BioSpectrum, a publication focused on the Asian
biotechnology industry. She then moved to the United States to pursue a master’s
degree in Science, Health and Environmental Reporting at New York University.
Manasi has reported primarily on topics that combine health and policy, and her
work has appeared in Nature Medicine, Nautilus and Scienceline. Her coverage at
BioPharm Insight focuses on cancer.