FDA Advisory Committee Backs Replimune's Twice-Rejected RP1 in Advanced Melanoma

FDA Advisory Committee Backs Replimune's Twice-Rejected RP1 in Advanced Melanoma

In a dramatic regulatory turnaround, the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 10 to 3 on July 30, 2026, in favor of Replimune Group's vusolimogene oderparepvec (RP1)¹ in combination with nivolumab (Opdivo) for adult patients with advanced melanoma who have progressed on a prior anti-PD-1-containing regimen.

The advisory committee was asked to address the critical question of whether the efficacy results from the single-arm Phase 2 IGNYTE trial (Study RPL-001-16) were evaluable and clinically meaningful, voting 10 to 3 in the affirmative. The committee also voted 10 to 3 that the benefit-risk profile of the combination therapy is favorable in this difficult-to-treat patient population.

A High-Stakes Stand-Off with FDA Reviewers

This positive panel vote comes despite highly critical briefing documents released by FDA staff on July 28, 2026, which characterized the IGNYTE data package as "not interpretable" due to its single-arm design, missing data, and patient retreatment protocols. The FDA had previously issued two Complete Response Letters (CRLs) for the RP1 biologics license application (BLA) in July 2025 and April 2026, primarily arguing that the single-arm trial could not be considered a well-controlled study.

Following a Type A alignment meeting in September 2025 and subsequent negotiations, the FDA accepted a third resubmission in June 2026 as a complete, Class I response, setting a Prescription Drug User Fee Act (PDUFA) target action date of August 2, 2026.

Clinical Background and Next Steps

The BLA is supported by the IGNYTE study, which evaluated RP1—an HSV-1–based oncolytic immunotherapy genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF—plus nivolumab. The trial reported an objective response rate (ORR) of 33.6% and a median duration of response of 24.8 months, with 15% of patients achieving complete remission.

Although the advisory committee's recommendation is nonbinding, the strong 10-3 endorsement significantly enhances the likelihood of an accelerated approval. If approved, the ongoing randomized Phase 3 IGNYTE-3 trial (NCT06264180), comparing RP1 plus nivolumab against physician's choice, is expected to serve as the confirmatory study required to support traditional approval. Per FDA guidelines, because the August 2 target action date fell on a Sunday, the official final regulatory decision from the agency is highly anticipated.