FDA CRL - Amgen Inc.

The FDA issued a Complete Response Letter (CRL) to Amgen Inc. for its Biologics License Application (BLA) 761062 for romosozumab, initially submitted on July 19, 2016. The application cannot be approved in its present form primarily due to significant safety concerns regarding cardiovascular risk associated with the drug. Studies 20110142 and 20110174 revealed a higher incidence of serious cardiovascular adverse events in patients treated with romosozumab compared to alendronate or placebo. These findings indicate a potential for increased cardiovascular risk, requiring a comprehensive review of all safety and efficacy data to ensure a complete benefit/risk assessment. The FDA noted that disparate findings across studies necessitate detailed analysis. To address these issues, Amgen must complete and submit final analyses for Studies 20110142 and 20110174, including individual clinical study reports and an integrated assessment of cardiovascular risk. This assessment must clearly articulate the basis for concluding that romosozumab's benefits outweigh its identified cardiovascular risks, supported by all pertinent narratives and datasets. Additionally, Amgen is required to provide a comprehensive safety update, detailing new findings, updated adverse event frequencies, trial discontinuations, and global safety experience. The FDA strongly recommends a meeting to discuss Amgen's detailed response plan before resubmitting the application, which must be a complete response within one year.