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News|Articles|July 29, 2026

FDA Questions RP1 Efficacy Ahead of Advisory Committee Vote on Melanoma Combination

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Key Takeaways

  • FDA reviewers judged the submission not “adequate and well-controlled,” emphasizing the absence of a control group and difficulty disentangling RP1 activity from concomitant nivolumab effects.
  • Response-assessment methodology was criticized for “artifactually” inflating primary objectives and response rates, calling into question the robustness of the reported efficacy signal.
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FDA staff have questioned RP1's melanoma trial data ahead of a July 30, 2026 advisory committee vote, causing Replimune shares to fall 30%.

FDA staff reviewers said in briefing documents released ahead of a July 30 advisory committee meeting that flaws in the design of Replimune's pivotal melanoma trial make it difficult to determine whether tumor shrinkage was driven by the company's oncolytic immunotherapy RP1 or by the checkpoint inhibitor it was combined with.1,2 Shares of Replimune fell roughly 30% in early trading following the documents' release, according to a report from Reuters.1

Key facts

  • Drug: RP1 (vusolimogene oderparepvec), proposed brand Tudriqev
  • Indication: Advanced melanoma, anti-PD-1-failed
  • Status: Third FDA review; 2 prior complete response letters (2025, 2026)
  • Meeting: FDA advisory committee vote, July 30, 2026
  • Efficacy claim: Company-reported ORR 33.6%, DOR 24.8 months

Replimune is seeking approval for RP1 (vusolimogene oderparepvec), proposed brand name Tudriqev, in combination with Bristol Myers Squibb's nivolumab (Opdivo) for adults with advanced melanoma that has progressed on prior anti-PD-1 therapy.1,3 In a statement to Reuters, the company said it looked forward to "a constructive dialogue about RP1's clinical meaningfulness" in this difficult-to-treat setting.1

What did FDA staff conclude in the briefing documents?

The FDA review team concluded that this biologics license application (BLA) "does not include an adequate and well-controlled investigation that demonstrates substantial evidence of effectiveness” and identified issues with response-assessment criteria that it said "artifactually" inflated the trial's main goals and response rates.1,2 The agency previously declined to approve RP1, first in July 2025, citing reliance on the single-arm IGNYTE trial without a control group and requesting additional data from a well-controlled study. Reuters reported FDA raised similar concerns in a second rejection in April 2026.1,4 A Cellular, Tissue, and Gene Therapies Advisory Committee meeting on the current resubmission is scheduled for July 30, 2026.2

Advanced melanoma is an aggressive form of skin cancer; a substantial proportion of patients do not respond to, or eventually progress on, anti-PD-1-based immunotherapy, leaving limited options for this population.1

How does RP1 work, and what efficacy data has Replimune reported?

RP1 is based on a proprietary herpes simplex virus strain engineered with a fusogenic protein (GALV-GP R-) and granulocyte-macrophage colony-stimulating factor (GM-CSF), designed to kill tumor cells directly while activating a systemic anti-tumor immune response.4 In data submitted with the current resubmission, Replimune reported an objective response rate of approximately 33.6% and a median duration of response of 24.8 months among patients with anti-PD-1-failed melanoma treated with RP1 plus nivolumab.3

How did analysts and the market react?

Reaction from Wall Street analysts was divided, according to Reuters. The outlet reported that BMO's Evan Seigerman said Replimune faces a difficult path forward and that FDA's current review appears consistent with the agency's earlier rejections, while J.P. Morgan's Anupam Rana said his firm's checks with physicians suggest strong support for RP1 within the melanoma community and that the company is likely to emphasize the drug's overall benefit-risk profile and the unmet need in refractory melanoma.1

What are the limitations and what comes next?

The advisory committee's July 30 vote on whether the IGNYTE data are evaluable and clinically meaningful is non-binding, and FDA is not required to follow the panel's recommendation.1 Neither Replimune nor Bristol Myers Squibb has disclosed additional efficacy or safety data beyond what is described in the briefing documents and prior public disclosures.

References

  1. Singh P. US FDA Staff Cast Doubt on Replimune Cancer Drug's Benefit; Shares Slide. Reuters. July 28, 2026. Accessed July 29, 2026. https://www.reuters.com/legal/litigation/us-fda-staff-raise-efficacy-concerns-replimunes-skin-cancer-drug-ahead-meeting-2026-07-28/
  2. FDA. FDA briefing document: BLA 125827, vusolimogene oderparepvec, Replimune, Inc. Cellular, Tissue, and Gene Therapies Advisory Committee meeting. Accessed July 29, 2026. https://www.fda.gov/media/193878/download
  3. Replimune. Advisory committee briefing materials: BLA 125827, TUDRIQEV (vusolimogene oderparepvec-wtpg, RP1). Cellular, Tissue, and Gene Therapies Advisory Committee Meeting. Accessed July 29, 2026. https://www.fda.gov/media/193879/download
  4. Replimune. Replimune receives complete response letter from FDA for RP1 biologics license application for the treatment of advanced melanoma. Press release. July 22, 2025. Accessed July 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics

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