FDA staff reiterated concerns that Replimune’s investigational RP1 program for melanoma lacks sufficient evidence to support approval. In briefing documents for a forthcoming advisory committee meeting, the agency criticized the pivotal trial design as inadequate to separate the drug’s efficacy from the background of prior PD-1 inhibitor exposure. The FDA also questioned whether locally injected RP1 produces systemic benefits, arguing that the single-arm study is not enough to evaluate the drug’s independent contribution to outcomes. Replimune responded that randomizing patients to RP1 versus placebo on top of PD-1 therapy is “not feasible or ethical” for patients whose cancer has stopped responding to PD-1 inhibitors, where no benefit from continued anti-PD-1 monotherapy has been established.