The FDA rejected Replimune’s oncolytic immunotherapy RP1 twice despite the program’s breakthrough therapy designation, according to reporting. The therapy is a modified herpesvirus injected directly into melanoma tumors to trigger cancer cell lysis and stimulate systemic immune responses. For patients with melanoma that doesn’t respond to traditional treatments, the lack of an approved second-line option has been a key gap, the report notes. Replimune’s clinical development timeline had suggested the FDA could move quickly, but the agency’s decisions introduce additional uncertainty around regulatory expectations for oncolytic virus therapies. The immediate industry focus shifts to what the FDA cited in the rejections—whether it relates to efficacy consistency, trial design, endpoint interpretation, or safety/benefit assessment—and what additional dataset or protocol amendments Replimune will pursue to restart a path to approval.