The FDA has rejected Replimune Group’s oncolytic virus therapy for advanced melanoma again, issuing a second complete response letter (CRL) for RP-1 (vusolimogene oderparepvec) after the company failed to resolve the agency’s concerns about the trial package. The latest decision follows the agency’s initial rejection in July and lands as Replimune faces renewed uncertainty on regulatory strategy and timelines. Replimune said its resubmission did not sufficiently address the FDA’s questions about results from the underlying study, reinforcing how tightly the agency is scrutinizing evidence supporting accelerated immuno-oncology approvals. The news sent shares down sharply around the relevant PDUFA timeline. The regulatory setback keeps the field’s attention on what constitutes “complete” evidence for oncolytic virus approaches in melanoma, where endpoints and comparability can drive approval decisions as much as safety signals. For biotech investors and clinical teams, the CRL underscores the operational and documentation burden needed for viral immunotherapies to clear the evidentiary bar in later-stage submissions.