The FDA twice declined to approve Replimune Group’s RP1, an oncolytic immunotherapy for melanoma previously granted breakthrough therapy status, raising fresh concerns for developers relying on accelerated regulatory pathways. Researchers and drugmakers said the denials were unexpected given RP1’s early-trial signal in patients with limited options. RP1 is injected directly into melanoma tumors using an engineered herpesvirus designed to trigger cancer cell lysis and subsequent immune activation. The article notes that FDA rejection halted what had been viewed as a likely near-term approval trajectory. UPMC Hillman Cancer Center director Yana Najjar described the unmet need for people left behind after traditional treatments fail, citing the lack of effective second-line options in some patient groups. Replimune CEO Sushil Patel said he had not seen the agency “behave like this,” underscoring heightened regulatory scrutiny for oncolytic products and the importance of addressing FDA concerns before resubmission.