We previously reported that Apotex filed a Citizen’s Petition requesting that FDA require biosimilar applicants to conduct comparative clinical efficacy studies in at least one intended patient population, rather than conducting such studies only in healthy subjects. Apotex noted in its petition that Coherus has filed an aBLA for a Neulasta biosimilar that relies on comparative data in healthy volunteers only.
Coherus recently filed a comment in response requesting that FDA deny Apotex’s petition. Coherus argues that clinical studies in intended patient populations are not universally required to establish biosimilarity because:
The standard is highly similar to the reference product demonstrated using sensitive analytical methods, and biosimilarity is confirmed but not established by limited subsequent clinical studies. Each step in the development of a biosimilar requires a head-to-head comparison between the biosimilar and the chosen 351(a) reference product – it is not between different indications for which the reference is used, nor between entirely different originator products containing different active ingredients, such as those discussed in the CP. And the better the analytical match, the fewer subsequent studies, including clinical, are expected because residual uncertainty has been minimized.
Coherus also argued that because comparative analytical data is “privileged to each [biosimilar] sponsor … each clinical confirmatory program will have been individually negotiated with the Agency,” and that previous FDA guidance established that “the better the match the more focused the clinical confirmatory program can be.”
Coherus further argued that previous FDA guidance has established that healthy volunteers is the appropriate population for pharmacokinetic and pharmacodynamic studies of biosimilars because such studies are “considered to be more sensitive in evaluating the product similarity because it is likely to produce less PK and/or PD variability compared with a study in patients with potential confounding factors such as underlying and/or concomitant disease and concomitant medications.”
According to Coherus, Apotex’s Petition puts too much emphasis on clinical studies relative to analytical comparisons for demonstrating biosimilarity. Rather, Coherus argues, “FDA has articulated that the basis of biosimilarity is an extremely clear analytical match, the best being referred to as ‘fingerprint-like.’ A biosimilar candidate without a good match can never be approved as biosimilar to a reference product regardless of how many clinical studies are conducted.”
Finally, Coherus asserts that FDA has emphasized the importance of analytical comparisons in its review of the biosimilars that have been approved to date:
In none of those instances has FDA required studies to be conducted in every population in which the reference product was approved. Furthermore, in all cases, FDA’s attention has been on the analytical match as the foundation of the agency’s “totality of evidence” approach  to FDA’s  determination of biosimilarity.”