FDA has again refused to move forward with Replimune’s oncolytic virus therapy for advanced melanoma, according to reports tied to another complete response letter. The agency said the company failed to resolve outstanding questions about the study results. The rejection follows the therapy’s July initial setback and has resurfaced debate over regulatory flexibility for oncology programs using complex trial designs and mechanistic rationales. Investors and patients remain focused on what data package Replimune can submit next to address FDA’s specific concerns. The repeated refusal keeps the drug’s path to approval uncertain and underscores how FDA scrutiny can persist even when companies pursue reconsideration after prior denials.