FDA issues complete response letter to Replimune for RP1 melanoma application

Replimune Group said it received a complete response letter from the U.S. Food and Drug Administration for its biologics license application for RP1 in combination with nivolumab for the treatment of advanced melanoma. The company said it disagrees with the FDA about whether the data set, upon which breakthrough therapy designation was awarded, is sufficient to allow the medicine to be made available to advanced cancer patients. The FDA said the evidence submitted does not meet the necessary standards for regulatory approval and that additional exploratory analysis did not change its prior conclusion that RP1 had no substantial evidence of effectiveness.

In the IGNYTE trial, patients with confirmed progression on an anti-PD-1 based regimen who received RP1 plus nivolumab had a 34% response rate with a median duration of 24.8 months with a favorable safety profile. The company also said median progression-free survival on RP1 plus nivolumab was 30.6 months in responding patients compared with 4.4 months on their prior PD-1 based regimen.

Replimune said that, with the complete response letter, it learned that a different review team was appointed for the resubmission and replaced the prior team who had interacted with the company. The company said the new team did not meet with it during the review process despite the company offering. It also said the agency appeared to have contradicted positions expressed at the September 2025 Type A meeting.

The company said that after testimony from melanoma experts, the agency did not raise further concerns about the heterogeneity of the patient population in IGNYTE and acknowledged that randomizing patients to an anti-PD1 only arm in the confirmatory study was not feasible. It said that, following an agency suggestion, it submitted a proposal for a descriptive analysis from IGNYTE-3 supporting contribution of components, requested feedback, and that the FDA did not respond and subsequently accepted the resubmission as a complete response to the July 2025 complete response letter.

Replimune said the FDA raised several points related to tumor assessment methodology. It said responses in IGNYTE were assessed using RECIST 1.1 without modifications, that analyses showed no material difference in response rates between injected and non-injected lesions, and that biopsies and surgical interventions did not impact tumor response.

Prior to the original BLA submission, the company said standard regulatory meetings were conducted to discuss trial design, patient population, and BLA package requirements. While a randomized controlled trial was preferred, the FDA suggested in the March 2021 Type B minutes that if the data was sufficiently compelling, a single-arm trial could be acceptable for consideration under accelerated approval. At the subsequent pre-BLA meeting, the FDA stated that it did not object to a BLA based primarily on data from the cohort of 140 patients in the Phase 2 IGNYTE trial who had advanced melanoma and progressed while being treated with prior anti-PD-1 based therapy; the company said the BLA was then accepted with breakthrough therapy designation and granted priority review.

The company said that, without timely accelerated approval, the development of RP1 will not be viable and that it will eliminate jobs, including substantially scaling back its U.S.-based manufacturing operations. Shares of Replimune fell 46% to $2.57 in after-hours trading after closing down 19% at $4.76, and the stock is down 51% this year.

Melanoma is the fifth most common cancer, with approximately 112,000 new cases estimated in the United States in 2026, and accounts for nearly 8,500 deaths annually. RP1, also known as vusolimogene oderparepvec, is Replimune’s lead product candidate.