FDA Approves Replimune’s Twice-Rejected Melanoma Drug

FDA granted accelerated approval on 6 August 2026 to Tudriqev (vusolimogene oderparepvec-wtpg), the engineered oncolytic virus Replimune spent nearly two years trying to get across the finish line under its development name, RP1. In combination with nivolumab, it is now approved for adults with unresectable advanced cutaneous melanoma who progressed on a prior anti-PD-1 antibody regimen — a population with few remaining options. The approval lands four days after the drug’s second target action date and closes out a review defined by two rejections, not one.

A virus as the active ingredient

Tudriqev is not a small molecule or an antibody; it is a genetically modified herpes simplex virus engineered to replicate selectively inside tumor cells, lyse them, and provoke an immune response against the cancer more broadly. It is injected directly into tumors — superficial lesions by needle, deep or visceral lesions under imaging guidance — and paired with intravenous nivolumab, a checkpoint inhibitor, on the theory that the localized viral attack primes a systemic immune response the checkpoint inhibitor then amplifies. The approved population is narrow and specific: adults with unresectable, advanced cutaneous melanoma whose disease has already progressed on an anti-PD-1-based regimen, a setting where treatment options run thin.

What the accelerated pathway actually requires

The approval rests on the single-arm IGNYTE trial: 140 patients with Stage IIIB, IIIC, or IV unresectable melanoma who had progressed on at least eight consecutive weeks of prior anti-PD-1 therapy. Ninety-one of them, with at least one non-injected lesion available to measure, made up the efficacy-evaluable population that produced the numbers behind this approval — a 24.2% objective response rate and a 14.1-month median duration of response. Those are surrogate endpoints, not survival data, which is why the approval is accelerated rather than standard: continued marketing is contingent on Replimune verifying clinical benefit in a confirmatory trial. That trial, IGNYTE-3, is already underway — a randomized, controlled Phase 3 study comparing Tudriqev plus nivolumab against treatment of physician's choice in patients who progressed on both anti-PD-1 and anti-CTLA-4 therapy, a harder-to-treat population than the one supporting today's approval.

The road here ran through two rejections

Replimune first submitted the BLA in late 2024. FDA issued a complete response letter on 21 July 2025, concluding the application lacked substantial evidence of effectiveness. Replimune resubmitted; FDA issued a second CRL in April 2026, reiterating the same concern. A third resubmission, filed in June 2026, was classified as a complete, Class 1 response — and this time FDA sent it to its Cellular, Tissue, and Gene Therapies Advisory Committee, which met on 30 July 2026 (a meeting Regulatory News covered when the notice first published) and voted 10-3 that the benefit-risk profile was favorable. The committee's vote came six days after FDA had already set 2 August as the PDUFA target date for that third submission; the approval itself arrived four days after that, on 6 August. For sponsors watching how FDA handles a second CRL on the same efficacy concern, the sequence matters as much as the outcome: an advisory committee airing the evidence in public, immediately ahead of the decision, is what changed the trajectory the third time.