Replimune gets third FDA rejection for melanoma drug RP1

Replimune’s melanoma drug RP1 has now been sent back by the FDA for a third time, an unusually prolonged review that puts the agency’s independence under a sharper public lens. The central question is no longer just whether the therapy can win approval, but whether the process was driven by scientific reconsideration or by pressure from outside the FDA.

The company disclosed on April 10, 2026 that the U.S. Food and Drug Administration issued a complete response letter for its biologics license application for RP1, known generically as vusolimogene oderparepvec, in combination with nivolumab for advanced melanoma. Replimune Group, Inc., based in Woburn, Massachusetts, has been pursuing the drug as a treatment for patients who progressed after anti-PD-1 therapy, a population the company says still faces limited options.

RP1 is an oncolytic immunotherapy, and Replimune has anchored its case on the IGNYTE study, which it describes as registration-directed. The anti-PD-1-failed melanoma cohort enrolled 141 patients and completed enrollment earlier this year. Replimune’s pipeline page lists the IGNYTE melanoma program action date as April 10, 2026, the same date the latest FDA rejection landed.

The company is not stopping there. Its confirmatory Phase 3 IGNYTE-3 trial in advanced melanoma is underway and enrolling, a sign that Replimune still sees a path to approval even after repeated setbacks. That parallel effort matters because it suggests the company is building a longer-term evidentiary record while the FDA continues to press on the product’s regulatory package.

The approval fight has unfolded alongside a steady stream of conference presentations. Replimune presented primary analysis data from IGNYTE, including initial biomarker analyses, at the 39th Annual Meeting of the Society for Immunotherapy of Cancer in Houston, Texas, and later returned with biomarker data and updated clinical results at the 40th annual meeting in National Harbor, Maryland. Those disclosures have kept the program in view even as the agency repeatedly declined to clear it.

For the FDA, a third rejection is not routine. It raises the stakes for how the agency explains its decisions, especially when outside attention is said to have played a role. Whether the final outcome turns on additional evidence, trial design, or political intervention, the RP1 case has become a test of how much independence the FDA can preserve when science and power collide.