The FDA has twice declined to approve Replimune Group’s oncolytic immunotherapy RP1 for melanoma, despite the program receiving breakthrough therapy designation and fast-track attention. Reporting highlighted a disconnect between early trial promise and the agency’s later approval hurdles. The article frames RP1 as a modified herpesvirus injected into melanoma tumors to trigger immune activation, with Yana Najjar of UPMC Hillman describing the treatment as potentially important for patients lacking effective second-line options. Replimune CEO Sushil Patel said he had not seen the agency “behave like this,” underscoring the intensity of the regulatory scrutiny. The piece emphasizes the uncertainty faced by sponsors when breakthrough pathways do not translate into approvals.