The FDA has twice declined to approve Replimune Group’s oncolytic immunotherapy candidate RP1 for melanoma, despite the program previously receiving breakthrough therapy designation based on earlier trial results. Researchers and developers have said the agency’s requests and review outcomes have been more restrictive than expected, leaving patients—particularly those with no effective second-line options—waiting for a potential new tumor-targeting approach. RP1 uses an engineered herpesvirus injected directly into melanoma tumors to trigger cancer-cell lysis and immune activation. Replimune CEO Sushil Patel said he has “never seen the agency behave like this.”