FDA Advisory Panel Backs Replimune’s RP1 for Advanced Melanoma

Replimune Group has secured an important regulatory milestone after the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 10 to 3 that the efficacy results from the Phase 2 IGNYTE trial evaluating RP1 (vusolimogene oderparepvec) in combination with nivolumab are evaluable and clinically meaningful for patients with advanced melanoma whose disease progressed after prior anti-PD-1 therapy.

The committee meeting reviewed Replimune’s resubmitted Biologics License Application (BLA) for RP1 plus nivolumab. Members considered whether the single-arm IGNYTE study could reliably determine treatment response and durability in the proposed patient population and whether the observed responses reflected clinically meaningful systemic antitumor activity attributable to RP1.

FDA Panel Supports Clinical Benefit in Difficult-to-Treat Melanoma

The positive advisory committee vote provides important external support for the efficacy evidence generated in IGNYTE, a study conducted in patients with advanced melanoma who had exhausted prior anti-PD-1 treatment options. This patient population has limited therapeutic choices and generally faces poor clinical outcomes following progression on immune checkpoint inhibitors.

Although FDA advisory committee recommendations are not binding, they often play an influential role during regulatory review. The agency is expected to complete its review of the BLA by the Prescription Drug User Fee Act (PDUFA) target action date of August 2, 2026.

RP1 Uses an Engineered Oncolytic Virus to Enhance Antitumor Immunity

RP1 (vusolimogene oderparepvec) is Replimune’s lead investigational oncolytic immunotherapy. It is derived from a proprietary strain of herpes simplex virus that has been genetically modified to increase direct tumor cell destruction while stimulating systemic immune responses.

The therapy expresses granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporates the fusogenic protein GALV-GP R-, which promotes enhanced tumor cell killing and may improve immune recognition of cancer cells beyond the injected tumor. Combined with nivolumab, a PD-1 immune checkpoint inhibitor, RP1 is intended to strengthen antitumor immune activity in patients with resistant disease.

IGNYTE Trial Findings Form the Basis of the BLA

The resubmitted BLA is supported by efficacy findings from the Phase 2 IGNYTE study, a single-arm clinical trial evaluating RP1 in combination with nivolumab in patients with advanced melanoma that had progressed after anti-PD-1 therapy.

During the advisory committee meeting, panel members examined whether the study’s design and conduct allowed reliable interpretation of objective response rates and durability of response. The committee ultimately concluded that the efficacy findings were both interpretable and clinically meaningful, voting 10 to 3 in favor of the application on the central efficacy question.

FDA Briefing Documents Raised Efficacy Questions Before the Meeting

The advisory committee’s recommendation contrasted with concerns outlined in the FDA’s briefing documents released before the meeting. FDA reviewers questioned whether the single-arm Phase 2 IGNYTE study could reliably establish treatment benefit in the absence of a randomized control arm and expressed uncertainty over whether the observed response rate and durability of response could be confidently attributed to RP1.

Following presentations from FDA reviewers, Replimune, independent experts, physicians, and patient representatives during the public meeting, committee members ultimately voted 10-3 that the efficacy results from IGNYTE were evaluable and clinically meaningful. Although the recommendation is not binding, it represents a notable shift from the skepticism reflected in the briefing materials and provides support for the ongoing BLA review.

Company Highlights Unmet Need Following Anti-PD-1 Failure

Following the meeting, Chief Executive Officer Sushil Patel, Ph.D., thanked committee members for their review of the IGNYTE data and acknowledged the patients and physicians who shared their experiences during the public hearing.

Patel noted that patients with advanced melanoma who progress after anti-PD-1 therapy continue to face a substantial unmet medical need and said the advisory committee outcome represents an important step toward expanding treatment options for this population.

Regulatory Decision Expected Within Days

With the advisory committee review completed, attention now shifts to the FDA’s final regulatory decision. The agency is scheduled to complete its review of the Class 1 BLA resubmission by August 2, 2026.

If approved, RP1 in combination with nivolumab could become a new treatment option for patients with advanced melanoma whose disease has progressed following prior anti-PD-1 therapy, potentially expanding the role of oncolytic immunotherapy in immunotherapy-resistant cancers.

What This Decision Means

If the FDA approves RP1 in combination with nivolumab, it could provide a new treatment option for patients with advanced melanoma whose disease has progressed after anti-PD-1 therapy, an area where effective therapies remain limited. While the advisory committee’s favorable vote strengthens the regulatory outlook, confirmatory randomized clinical data will still be important to validate the long-term clinical benefit and define the therapy’s role in routine oncology practice.

References

Replimune Announces Favorable Outcome of FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee Meeting for RP1 in Advanced Melanoma | Replimune Group Inc.