Biosimilars approved for hematology use: lessons from comparative efficacy studies and comparative analytical assessments.

Biosimilars used in hematology have been at the forefront of biosimilar development since the first US approval in 2015 of a filgrastim product, with >80 now licensed by the US Food and Drug Administration (FDA). Developers traditionally submitted data from a comparative analytical assessment (CAA) and clinical studies, often including a comparative efficacy study (CES), to support demonstrating their product is "highly similar" to and has "no clinically meaningful differences" from its reference product (RP). However, growing scientific confidence in the analytical comparisons between biosimilars and their RP included in the CAA has prompted the FDA and global regulators to reconsider the utility of CESs. Recently, the FDA published updated recommendations on the need for a CES in biosimilar programs. As approvals for hematologic biosimilars span the entire history of FDA biosimilar development across a breadth of patient ages and diseases, reexamining these programs provides valuable insights into the evolving role of the CES in the past and its role in the future. In this review, we present a historical overview of the development programs for all FDA-approved hematologic biosimilars in the context of an emerging global consensus recognizing that the CAA is more sensitive than the CES for predicting biosimilarity.