The FDA issued a complete response letter rejecting Replimune Group’s Biologics License Application for RP1, an oncolytic virus therapy combined with nivolumab for advanced melanoma. The agency cited inadequacies in the confirmatory phase 3 trial design and heterogeneity in patient population as key concerns that undermined evidence of effectiveness. The decision resulted in a drastic 75% drop in Replimune's stock price. The company expressed surprise, noting prior agency alignment on the confirmatory study design. This rejection highlights increasing regulatory scrutiny and evolving standards impacting clinical trial requirements.