FDA briefing documents for Replimune’s melanoma drug RP1 highlighted lingering concerns that the company’s single-arm IGNYTE study could not clearly prove the treatment’s benefit, especially without an Opdivo-only control group.
FDA reviewers said the way responses were measured may have inflated the apparent efficacy, and that they could not reliably tell whether tumor shrinkage came from RP1, nivolumab, or local injection effects.
Replimune argued the study was the best feasible design because it would be unethical and impractical to randomize patients to anti-PD-1 monotherapy when there is no evidence it helps after PD-1 failure.
The company also said the FDA’s rejection conflicted with positions the agency had previously expressed in meetings, while FDA staff maintained that the application lacked adequate and well-controlled evidence.
An FDA advisory committee later voted 10-3 that the IGNYTE results were evaluable and clinically meaningful, but the earlier staff critique showed the internal split between the company’s interpretation and regulators’ concerns.
The dispute centered on whether the data package was sufficient for accelerated approval of RP1 plus nivolumab for advanced melanoma, with FDA staff warning the overall survival analysis was not interpretable.
Sources:
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