The FDA’s biosimilar pathway has encouraged a robust product pipeline, but the fact that few biosimilar drugs have been approved by the agency thus far means that there is still some industry uncertainty on the FDA’s approach to this class of products.
The FDA’s biosimilar pathway has encouraged a robust product pipeline, but the fact that few biosimilar drugs have been approved by the agency thus far, as well as the fact that the FDA has yet to finalize its guidance concerning the demonstration of interchangeability for biosimilars, means that there is still some industry uncertainty on the FDA’s approach to this class of products.
Pharma Intelligence, in a review of agency documents concerning US biosimilar applications, has highlighted lessons learned from the first 4 biosimilars to gain FDA approval: Amgen’s adalimumab (Amjevita), Sandoz’s etanercept (Erelzi), Celltrion’s infliximab (Inflectra), and Sandoz’s filgrastim (Zarxio).
The naming conventions for biosimilars, the review points out, have been a significant challenge for biosimilar applicants. When the FDA announced its final guidance on the naming of biologics and biosimilars in January 2017, it elected to use a system in which a 4-letter suffix, devoid of meaning, is appended to the reference product’s nonproprietary name. Under the guidance, an applicant is instructed to submit up to 10 proposed suffixes for the drug, in order of the applicant’s preference, with accompanying supportive information about the merits of those suffixes.
As Pharma Intelligence points out, biosimilar applicants should be prepared to undergo a rigorous, data-driven vetting of their proposed suffixes to demonstrate that their choices do not create confusion or pose a risk of errors. However, the agency may be willing to consider flexibility with respect to which meaningless suffix is appended to a biosimilar’s name; just as Amgen was able to convince the FDA that its suffix of choice (-atto) was preferable to other options for its adalimumab product, future biosimilar developers may also attempt to provide persuasive rationales for their suffixes of choice.
Labeling, too, has proven to be a challenging area for biosimilar applicants. The review notes that the FDA has been wary of allowing a biosimilar product’s label to diverge from that of its reference. Celltrion, the authors note, failed in its attempt to include data on adverse events, pharmacokinetics, and clinical studies that were specific to its infliximab product and not to the reference Remicade. Sandoz was also prevented from making amendments to its labeling that would allow the company to note differences in its product presentation from that of the reference product.
Finally, the review notes that the FDA’s programs to incentivize the development of pediatric drugs has posed a hurdle—while innovator products may hold waivers concerning pediatric studies, biosimilar products may still be required to conduct such studies. Sandoz, for example, was asked by the FDA to provide data from pediatric studies with etanercept. The agency eventually demonstrated what the review calls “a degree of regulatory flexibility,” however, and allowed the biosimilar etanercept’s label to indicate that efficacy and safety of the product in the treatment of pediatric psoriasis had not been established.
As the next wave of biosimilar manufacturers file their abbreviated Biologics License Application, the experience of biosimilar developers thus far could prove particularly useful. With only a 40% approval rate for first-cycle applications, the industry has room to learn from—and improve upon—its growing body of experience.