An Expert Discussion: Lessons Learned and the Future of Biosimilar Uptake

At the 8th Annual Summit on Biosimilars, a panel of legal experts reviewed lessons learned from the first 18 months of biosimilars in the United States, and looked ahead to the question of how these drugs will gain acceptance and market uptake.

In describing trends in the approval process for biosimilars, Kevin Noonan, partner at McDonnell Boehnen Hulbert & Berghoff LLP, noted that clinical data provided for biosimilar products has become more extensive with each Biologics License Application (BLA). Whereas the data Sandoz provided for its filgrastim biosimilar (Zarxio) comprised 4 pharmacokinetic (PK) studies and 5 animal studies, earning the first US biosimilar approval for all indications of its reference product, Samsung Bioepis’ infliximab biosimilar (Renflexis), the most recent biosimilar to receive approval, relied on 11 double-blind parallel studies and 2 PK studies to receive approval for all indications of its reference product. Noonan noted that Pfizer’s epoetin biosimilar (Retacrit), which is expected to be the 6th approved US biosimilar, has undergone physiochemical characterization, biological characterization, clinical PK and pharmacodynamic (PD) studies, 2 comparative safety and efficacy studies, and 2 long-term safety studies.

The growing bodies of data provided to the FDA suggest a trend among biosimilar manufacturers seeking to ensure (and speed) their products’ approvals; biosimilars currently under development may well produce data from an equally substantial—or even greater—number of studies to gain timely FDA approval.

In the days ahead, the marketplace could expect to see such robust studies from manufacturers developing treatments modeled on the top-earning US biologics. The panelists highlighted some of these top grossers:

• aflibercept (Eylea, used to treat age-related macular degeneration)
• eculizumab (Solaris, used to treat paroxysmal nocturnal hemoglobinuria)
• ustekinumab (Stelara, used to treat plaque psoriasis and psoriatic arthritis)
• ranibizumab (Lucentis, used to treat age-related macular degeneration, macular edema, and diabetic retinopathy)
• abatacept (Orencia, used to treat autoimmune diseases including rheumatoid arthritis)
• pertuzumab (Perjecta, a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer)
• tocilizumab (Acterma, used to treat moderate to severe rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis)

While a wealth of clinical data may be enough to persuade the FDA to approve a biosimilar to these reference products, the panel was divided over whether even the most thoroughly tested products would see significant uptake in the United States. Aaron Lukas, member of Cozen O’Connor, expressed his view that, until interchangeability has been demonstrated for biosimilar products, patient populations will not be switched from references treatments to biosimilars. Innovators and biosimilar manufactures will compete over newly diagnosed patients, he said, not over existing patients.

Others in the room disagreed with Lukas’ assessment, noting that payers such as the US Department of Veteran Affairs could very well seek to switch patients to biosimilars if a substantial cost savings is possible, and that switching studies could be used to help reassure patients of biosimilars’ safety and efficacy.

Noonan added that physicians will have a unique role to play in the question of acceptance. While pharmacists have traditionally driven uptake of generic drugs due to the better margins they receive on such products, biologics are frequently physician-administered; physicians, not pharmacists, Noonan indicated, will have to drive uptake.

It remains to be seen whether the US market will indeed prove hospitable to biosimilars, but evidence from Europe demonstrates that patient education has led to greater patient acceptance of biosimilars without demonstrated interchangeability. Increased education of patients and providers about the safety and efficacy biosimilars, may hold the key to driving greater and swifter uptake.