Reversal After Two Rejections: FDA Grants Accelerated Approval to Oncolytic Virus Therapy for Advanced Melanoma

After advanced melanoma stops responding to immune checkpoint inhibitors, treatment options rapidly narrow. The U.S. Food and Drug Administration (FDA) has now granted accelerated approval to Replimune’s Tudriqev (vusolimogene oderparepvec-wtpg, formerly known as RP1) in combination with nivolumab for adults with advanced cutaneous melanoma that cannot be surgically removed and has continued to progress after anti-PD-1 therapy.

Tudriqev is an oncolytic immunotherapy based on a genetically modified herpes simplex virus type 1. It is injected directly into tumors, causing cancer cells to rupture and release antigens while seeking to trigger a broader immune response. Combined with the PD-1 blocker nivolumab, it aims to re-engage the immune system in recognizing and attacking tumors after prior immunotherapy has failed.

The approval is based on 91 efficacy-evaluable patients in the IGNYTE trial. According to data released by the company, the objective response rate was 24.2%, meaning that tumors shrank by a predefined amount in about one-quarter of patients; the median duration of response was 14.1 months. These results suggest that some patients may achieve durable disease control, but they do not establish that everyone will benefit.

The controversy stems from the structure of the evidence. IGNYTE is a single-arm study without a randomized control group, and all patients received Tudriqev with nivolumab, making it difficult to clearly distinguish how much of the efficacy came from the new therapy, nivolumab, or differences among patients. The FDA previously rejected the application twice, and reviewers had also questioned the study design, how it was conducted, and Tudriqev’s independent contribution to the combination therapy. An advisory committee subsequently concluded that the efficacy signal and unmet medical need were sufficient to support limited access.

The safety analysis included 140 treated patients, of whom 35% experienced serious adverse reactions and 2.9% permanently discontinued Tudriqev because of adverse reactions. These figures cannot be interpreted simply alongside the response rate; consideration must also be given to the patients’ pre-existing advanced disease, prior treatments, and the immune-related risks that nivolumab itself may pose.

Accelerated approval means Tudriqev can now enter the U.S. market, but it does not mean the efficacy debate is over. Continued approval may depend on whether the ongoing randomized, controlled Phase 3 IGNYTE-3 trial confirms clinical benefit; if verification fails, the FDA may still require the indication to be modified or the product to be withdrawn. The trial will also more directly test whether adding Tudriqev to nivolumab is genuinely superior to existing treatments selected by physicians.

Access to treatment presents another hurdle. According to company information cited by STAT, Tudriqev is priced at $450,000 per course of treatment, before rebates and discounts. For patients and payers, the approval creates a new treatment pathway while leaving a sharper question for the confirmatory trial: amid the high cost and continuing uncertainty in the evidence, which patients can truly obtain benefits substantial enough to alter the course of their disease?