Replimune receives FDA complete response letter for RP1 plus nivolumab in advanced melanoma, cites review team change, prior Type B meeting discussions, and IGNYTE trial data supporting efficacy.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Replimune Group announced that the U.S. Food and Drug Administration has issued a complete response letter for its biologics license application seeking approval of RP1 in combination with nivolumab for patients with advanced melanoma. The submission was primarily based on results from the Phase 2 IGNYTE trial in patients who progressed after anti-PD-1–based therapy.
In the IGNYTE trial, RP1 plus nivolumab demonstrated a 34% response rate with a median duration of response of 24.8 months and a favorable safety profile. The dataset had previously supported breakthrough therapy designation, but the FDA determined the evidence was not sufficient for approval.
Replimune said the review team assigned to the resubmission was different from the FDA review team that had previously interacted with the company, and no meetings were held during the review despite the company offering to engage. A senior member of the earlier review team had publicly stated that the clinical team believed adequate evidence supported the contribution of RP1 plus nivolumab, but leadership did not agree.
The company also said the agency’s position differed from earlier discussions. After testimony from melanoma experts, the FDA had not raised further concerns about heterogeneity in the IGNYTE patient population and acknowledged that randomizing patients to an anti-PD-1–only arm in a confirmatory study was not feasible.
Replimune also submitted a descriptive analysis proposal from IGNYTE-3 and included data showing median progression-free survival of 30.6 months with RP1 plus nivolumab versus 4.4 months on prior PD-1 therapy but said the agency did not provide feedback.
The CRL also referenced tumor assessment methodology. Replimune stated that responses in IGNYTE were assessed using RECIST 1.1 as requested, and analyses showed no meaningful difference between injected and non-injected lesions. Additional analyses indicated biopsies and surgical procedures did not affect tumor response.
The company further noted that during a March 2021 Type B meeting with the FDA, the agency indicated that while a randomized controlled trial was preferred, a single-arm study could be considered for accelerated approval if the data were compelling.
At a later pre-BLA meeting, the FDA did not object to submitting the application primarily based on the Phase 2 IGNYTE cohort. The BLA was subsequently accepted with breakthrough therapy designation and priority review, and the company initiated the Phase 3 IGNYTE-3 trial as a confirmatory study.
CEO Sushil Patel said the company was disappointed with the decision and emphasized that the treatment showed strong efficacy with a favorable safety profile for patients with limited options. He added that without accelerated approval, further development of RP1 would not be viable and the company plans to eliminate jobs and significantly scale back U.S. manufacturing operations.
RP1 (vusolimogene oderparepvec) is an engineered herpes simplex virus–based oncolytic immunotherapy designed to increase tumor killing and stimulate systemic anti-tumor immune responses through expression of a fusogenic protein and GM-CSF.
Reference
Replimune Receives Complete Response Letter from the FDA for RP1 Biologics License Application for the Treatment of Advanced Melanoma, 10 April 2026, https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics-0
About the Writer
Nikita Jha BPharm is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.