Replimune receives CRL
The FDA issued a Complete Response Letter for Replimune’s RP1 plus nivolumab in advanced melanoma, saying the single‑arm IGNYTE data and heterogeneous population made it impossible to isolate RP1's contribution. The agency raised no safety concerns but indicated a controlled trial such as IGNYTE‑3 would be needed, with data timing noted for 2027. (x.com)
The Food and Drug Administration rejected Replimune’s melanoma filing again on April 10, leaving RP1 without a U.S. approval path this year. (open.fda.gov) The agency’s letter said Replimune’s application relied on a 140-patient, single-arm Phase 2 study called IGNYTE, with no concurrent control group for the main tumor-response endpoint. Food and Drug Administration reviewers wrote that the trial could not show how much benefit came from RP1 itself when it was given with nivolumab. (open.fda.gov) Food and Drug Administration reviewers also cited a mixed patient population and uncertainty in response assessments, including surgical procedures that could have affected how tumor shrinkage was counted. For Replimune’s separate Phase 3 study, IGNYTE-3, the agency said only about 10% of the planned population had been treated so far. (open.fda.gov) RP1 is an oncolytic immunotherapy, a treatment built from a modified virus that is injected into tumors to kill cancer cells and help the immune system recognize them. Replimune says RP1 is based on herpes simplex virus type 1 and is engineered to carry granulocyte-macrophage colony-stimulating factor, or GM-CSF, and a fusion protein meant to intensify tumor-cell killing. (sec.gov) Nivolumab, sold as Opdivo, is an immune checkpoint blocker that releases a brake on T cells, the white blood cells that attack cancer. Replimune tested the combination in adults with unresectable advanced cutaneous melanoma whose disease had already progressed on a programmed death receptor-1, or PD-1, blocking drug. (open.fda.gov) The company’s pitch to regulators was that IGNYTE showed a 32.9% objective response rate, a 15.0% complete response rate, and a median duration of response of 33.7 months in 140 patients whose melanoma had failed prior anti-PD-1 treatment. Those numbers came from a blinded central review in an update presented in late 2025. (jitc.bmj.com) But the Food and Drug Administration has now twice concluded that the study design does not meet the standard for proving effectiveness. Replimune received its first Complete Response Letter on July 21, 2025, resubmitted the application, and the agency accepted that resubmission on October 20, 2025 with an April 10, 2026 action date. (sec.gov 1) (sec.gov 2) A Complete Response Letter is the Food and Drug Administration’s formal notice that it will not approve an application in its current form. In this case, the agency did not raise new safety problems in the public letter; the dispute was over whether the evidence was strong enough to show the drug works. (open.fda.gov) (sec.gov) That shifts attention to IGNYTE-3, the randomized Phase 3 trial Replimune started on July 11, 2024. The study is recruiting about 400 patients and compares vusolimogene oderparepvec plus nivolumab against physician’s choice of treatment, with estimated primary completion in January 2029. (clinicaltrials.gov) Replimune said after the first rejection in July 2025 that it was “surprised” and believed RP1 plus nivolumab could help patients with few options. For now, the Food and Drug Administration’s second no leaves the company waiting for controlled-trial data instead of a near-term approval. (sec.gov)
