The Food and Drug Administration has found the data package submitted by Replimune for its oncolytic immunotherapy, vusolimogene oderparepvec (RP1), to be "not interpretable," setting up a challenging advisory committee meeting this week, according to documents released July 28.
Replimune's submission was based on a single-arm mid-stage study intended to support accelerated approval of RP1 in combination with Bristol Myers Squibb’s PD-1 inhibitor Opdivo for adults with unresectable advanced cutaneous melanoma who have experienced disease progression after anti-PD-1 therapy. The FDA has previously rejected the application twice, most recently issuing complete response letters citing concerns about the trial design and lack of adequate controls.
In briefing documents published ahead of Thursday’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) meeting, FDA reviewers said that the response assessment used in the Phase 1/2 IGNYTE study “confounds interpretation of the reported efficacy results and limits FDA’s ability to verify the reported results.” The agency also wrote that objective response data from the single-arm trial “are not of sufficient magnitude to overcome concerns” about efficacy. According to reviewers, without a reliable historical control group, it cannot be determined whether RP1 contributes meaningfully when combined with Opdivo. "The overall survival analysis from the single-arm IGNYTE study is not interpretable," FDA staff wrote.
Replimune argued in its own briefing document that conducting a randomized trial would be unethical for this patient population: “It is not feasible or ethical to randomize this patient population to a comparator arm of anti-PD-1 monotherapy that offered no hope for response... therefore a study comparing RP1 in combination with nivolumab, to nivolumab monotherapy in patients whose disease progressed while on nivolumab or other anti-PD-1 was not conducted.” The company further explained that at the time IGNYTE was performed there were no treatments available for patients who had progressed after anti-PD-1 treatment and little literature evaluating such scenarios.
Replimune noted that previous approvals for similar indications were granted based on single-arm studies—such as Iovance Biotherapeutics’ Amtagvi approval in 2024—but acknowledged that regulators have consistently disagreed with their approach. In prior complete response letters issued in July 2025 and April 2026, FDA reiterated objections regarding trial design and advised against seeking approval based solely on single-arm studies.
The CTGTAC will vote Thursday on whether efficacy results from IGNYTE are evaluable and clinically meaningful. While analysts say panel composition could influence discussion outcomes, ultimate approval rests with FDA officials.
