Systematic Review Identifies 6 Trends in US Biosimilar Approvals

The Center for Biosimilars Staff

Because biosimilars are relatively new to the United States, drug makers pursuing FDA approval for biosimilars seek additional information about the kinds and quantities of evidence that the agency uses to approve these therapies.

The European Union has swiftly outpaced the United States in the number of biosimilar therapies that it has approved for marketing; the FDA has only approved 7 biosimilars to date, though many additional molecules are being developed with the US market in mind. Because biosimilars are relatively new to the United States, drug makers pursuing FDA approval for biosimilars seek additional information about the kinds and quantities of evidence that the agency uses to approve these therapies.

A new review, appearing in the Journal of Managed Care and Specialty Pharmacy, assesses the evidence that was used in the first 5 biosimilar approvals: filgrastim-sndz (Zarxio), infliximab-dybb (Inflectra), adalimumab-atto (Amjevita), etanercept-szzs (Erelzi), and infliximab-abda (Renflexis). The review draws on data derived from drug-specific FDA approval documents, webcasts, and advisory committee votes; reference product information; evidence used for the extrapolation of indications; and evidence used to demonstrate similarity in terms of analytic and functional characteristics, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety, and immunogenicity.

The review’s authors identified 6 key issues from their data:

  • The types of evidence that the FDA evaluated when approving each product ranged from many analytical studies to few clinical studies. The researchers note that this finding is reflective of the agency’s “totality of the evidence” approach to demonstrating biosimilarity.

  • All manufacturers used 3-way bridging studies (which allow a biosimilar developer to use data from a product licensed in another locality to indirectly demonstrate similarity between the proposed molecule and a US-licensed drug) when seeking the FDA’s approval.

  • Many indications of the approved biosimilars were granted on the basis of extrapolation, the scientific justification for which often includes the mechanism of action in each indication for which licensure is sought. PK and immunogenicity in different patient populations, as well as the toxicity profile for each indication and patient population, are also often included in the scientific justification.

  • The majority of formulations of approved biosimilars were the same (or nearly the same) as those of their references, a finding that may bear a relationship to the FDA’s position that biosimilars with formulations not identical to those of the reference may not be granted interchangeable status. Some discrepancies existed, however, such as Amjevita’s auto-injector device that contrasted with the reference Humira’s pre-filled pen, and the presence of a needle guard for Erelzi.

  • The biosimilars were not always approved for all indications of their reference products for 2 reasons: first, some reference drugs were granted new indications after biosimilar approval, and second, some reference product indications were protected by marketing exclusivity.

  • None of the approved biosimilars were granted an interchangeable status, since the FDA has not yet finalized its process for demonstrating interchangeability.

Finally, the authors note that FDA advisory committee meetings may be slowing the process of biosimilar approval, and suggest that only those biosimilars that have “specific issues” that would warrant convening a committee be subject to such proceedings. The review identifies a second challenge specific to US biosimilar uptake: the long interval between product approval and market availability, which is a phenomenon largely tied to lengthy patent litigation between reference product sponsors and biosimilar developers.