Biopharmaceutical Report II
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 thoug h 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.
Interchangeability is not done at the pharmacist level as a physician’s approval is still required for biosimilar use
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 FDArecognized 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 has a Masters 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 Masters 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.