The FDA has rejected Replimune Group’s engineered oncolytic virus therapy, RP-1, for advanced melanoma for a second time, escalating scrutiny of the dataset behind the application. The decision follows an earlier rejection in July, when the agency cited unresolved doubts about study results. Replimune had sought reconsideration after that first FDA complete response, but the agency again concluded the company did not address key issues with the evidence submitted. The repeated rejection keeps the therapy in regulatory limbo just as melanoma developers compete to differentiate immunotherapy approaches. For investors and developers, the case highlights how the FDA is applying consistent expectations to supplemental submissions and resubmitted analyses when endpoints and interpretation remain contested.