The FDA rejected Replimune Group’s oncolytic immunotherapy RP1 twice despite earlier ‘breakthrough therapy’ designation based on promising trials in melanoma. The company is still pursuing approval after the agency’s decisions disrupted expectations for a fast route to market. RP1 is an engineered herpesvirus injected directly into melanoma tumors, designed to burst cancer cells and provoke systemic immune activity against tumor cells. Replimune CEO Sushil Patel said he had never seen the agency act “like this,” underscoring the tension between designation status and ultimate regulatory outcomes. Researchers and developers are left reassessing what the agency is requiring for the remaining approval path in a setting with limited second-line options for some melanoma patients.