Coherus Biosciences, Inc. – FDA CRL

Coherus BioSciences, Inc. received a Complete Response Letter (CRL) from the FDA for its Biologics License Application (BLA 761039) for CHS-1701, a proposed biosimilar, submitted under section 351(k) of the Public Health Service Act. The application cannot be approved in its current form primarily due to immunogenicity concerns. The FDA highlighted an observed higher incidence of treatment-emergent persistent anti-drug antibodies (ADA) in the CHS-1701 arm (9.8%) compared to US-licensed Neulasta (5.8% per FDA analysis). This difference, exceeding a 10% threshold, creates residual uncertainty regarding biosimilarity and potential clinically meaningful differences. Additionally, the BLA lacked sufficient data on anti-G-CSF antibody titers and the incidence of neutralizing antibodies (NAb). Furthermore, both neutralizing antibody assays submitted were deemed inadequate. Issues included unacceptable assay variability, incorrect drug concentrations, lack of supporting data for critical assay parameters, insufficient sensitivity, and improper determination and verification of assay cut-points using appropriate study samples. To address these issues, Coherus must provide further data clarifying the nature of the ADA response (anti-PEG vs. anti-G-CSF), including anti-G-CSF titers and comprehensive NAb testing of positive samples. Crucially, a fully validated neutralizing antibody assay, compliant with FDA guidance, is required to adequately assess NAb in clinical samples. Depending on the new data, further clinical studies may be necessary to ensure no clinically meaningful differences between CHS-1701 and Neulasta.