The FDA has declined to approve Replimune’s biologics license application for vusolimogene oderparepvec in combination with nivolumab for adults with unresectable advanced cutaneous melanoma.
The agency first rejected the application in a July 21, 2025, complete response letter and reaffirmed that decision in a second complete response letter issued April 10, after reviewing additional analyses from the company’s phase 2 RPL-001-16 study and ongoing phase 3 RP1-104 trial. FDA reviewers said the updated data still did not provide sufficient evidence of effectiveness.
The FDA also said the RP1-104 analysis included only 10% of the planned 400-patient study population, with 22 patients in the investigational arm and 18 in the control arm. Additional concerns included a lack of duration-of-response data and progression-free survival analyses that were not prespecified.
The agency said the single-arm RPL-001-16 trial was not considered an adequate and well-controlled clinical investigation. FDA reviewers identified multiple issues with tumor response assessments, including surgical interventions and retreatment decisions that may have confounded efficacy results.
The decision drew criticism from some oncologists involved in the trial.
“It was devastating news,” Trisha Wise-Draper, MD, a dermatologist at the University of Cincinnati who had patients enrolled in the trial, told KFF Health News. Eric Whitman, MD, medical director of Atlantic Health System’s oncology service, said that the treatment could have affected outcomes for “maybe 2,000 patients.”
The FDA told Replimune it must conduct additional adequate and well-controlled clinical trials to support approval. The company has one year to resubmit or withdraw the application.
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