FDA Advisory Committee Backs Replimune's RP1 Melanoma Therapy in 10-3 Vote After Two Prior Rejections
An FDA panel voted 10-3 that IGNYTE trial results for RP1 plus nivolumab are clinically meaningful, days ahead of an August 2 decision.
Overview
An FDA advisory committee voted 10 to 3 on July 30 that efficacy results from Replimune’s IGNYTE trial are “evaluable and clinically meaningful,” backing the company’s oncolytic virus therapy RP1 for advanced melanoma after two prior rejections of the same application, according to Replimune. The vote, delivered by the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee, does not itself constitute approval, but it clears a path toward the agency’s next decision on the drug, due August 2, according to StockTitan.
What the Committee Voted On
The advisory committee addressed the Biologics License Application (BLA) resubmission for RP1, known generically as vusolimogene oderparepvec, in combination with the checkpoint inhibitor nivolumab for treating advanced melanoma in patients who progressed on prior anti-PD-1 therapy, according to Replimune. The panel addressed whether the single-arm IGNYTE study, as designed and conducted, allows reliable determination of expected response rate and durability in the proposed population, and whether observed responses demonstrate clinical meaningfulness and systemic antitumor activity attributable to RP1, per Replimune. Committee members voted 10 to 3 on the specific question: “Are the efficacy results from IGNYTE evaluable and clinically meaningful?” according to Replimune.
The vote was far from unanimous, and panelists on both sides voiced reservations about the underlying data even as most ultimately backed it. Lawrence Schwartz, chair of radiology at Memorial Sloan Kettering, acknowledged “This is messy data,” while still voting yes, according to BioSpace. Among the dissenters, patient representative Diane Aronson said “Hope is important, but reality weighed into my vote,” citing concerns about the study’s science and confusion over RECIST response criteria, per BioSpace. FDA associate director of clinical programs Sundeep Agrawal pressed the agency’s core objection, saying “contribution of effect and the need for each product has not been demonstrated,” according to BioSpace. Two other committee members flagged similar doubts: Karla Ballman, a biostatistics consultant, said “There is so much uncertainty to what that overall response rate is,” while Melinda L. Yushak of Emory University said “We do need the phase 3 data to fully answer this question,” according to CancerNetwork.
A Third Attempt After Two Rejections
The advisory committee vote caps a difficult, multi-year regulatory path for RP1. The FDA issued a first Complete Response Letter in July 2025, and a second one in April 2026, with the agency citing trial design as the primary grounds for rejection both times, according to BioSpace. Replimune’s application traces back further still: the FDA granted RP1 breakthrough therapy designation in November 2024 and accepted it for priority review in January 2025, before the first rejection, according to CancerNetwork. The company’s third resubmission was accepted in June 2026, setting up the July 30 advisory committee meeting and the current August 2 target action date under a Class 1 review timeline, per CancerNetwork.
As previously reported by The Machine Herald, Replimune presented three-year survival data from IGNYTE at the American Society of Clinical Oncology’s annual meeting in May, a day after announcing it had aligned with the FDA on a path toward this third submission. The trial enrolled 140 patients with advanced melanoma who had progressed on prior anti-PD-1 therapy and required at least eight weeks of that prior therapy with confirmed progression, according to CancerNetwork. The combination produced an objective response rate of 33.6% under modified RECIST v1.1 criteria and a complete response rate of 15.0%, with median overall survival of 32.9 months and one-, two-, and three-year overall survival rates of 75.3%, 61.5%, and 47.8% respectively, per CancerNetwork. Treatment-related adverse effects of any grade occurred in 88.7% of participants, most commonly chills, fatigue, pyrexia, and nausea, while grade 3/4 effects occurred in 12.8% of patients and no grade 5 events were reported, according to CancerNetwork.
Company Response
Replimune CEO Sushil Patel welcomed the outcome. “We are encouraged by today’s outcome and would like to thank the committee for its thoughtful discussion of the IGNYTE data,” he said, adding, “This is an important step forward for patients with advanced melanoma who have progressed on anti-PD-1 therapy,” according to Replimune.
What We Don’t Know
The advisory committee’s favorable vote does not constitute FDA approval — it supports continued regulatory review of the BLA resubmission, according to StockTitan. The FDA is not obligated to follow its advisory committees’ recommendations, and given that the agency has twice rejected RP1’s application on trial-design grounds even as members of its own review staff continued to question whether the drug’s individual contribution to the combination’s effect had been demonstrated, the outcome of the August 2 decision remains uncertain. Neither Replimune nor its outlets covering the meeting have indicated what additional analyses, if any, the FDA requested following the vote.