The FDA rejected Replimune’s oncolytic virus therapy RP-1 for advanced melanoma for a second time, according to multiple reports citing the agency’s rationale around unresolved trial doubts. The latest action follows an earlier complete response letter (CRL) and comes as the company had been pushing for reconsideration after a first rejection in July. Replimune has positioned vusolimogene oderparepvec as an immune-stimulating approach, but regulators have continued to question aspects of the study package. The repeated decision reinforces how tightly the biologics review bar is being applied to oncolytic virus data, particularly when efficacy, endpoints, and interpretability issues are still under dispute. For investors, the immediate read-through is heightened regulatory timing risk for late-stage viral immunotherapies until the FDA issues a clear path forward. For developers, it also underscores that addressing agency concerns in a resubmission may require more than protocol or narrative updates—potentially extending into additional evidence. The FDA’s decision is a near-term commercial and development setback for Replimune and keeps the melanoma market waiting on an alternative mechanism beyond checkpoint-based strategies.