Three submissions, two rejections, one public fight with the FDA, and, finally, an approval. On August 6, 2026, the U.S. Food and Drug Administration granted accelerated approval to Tudriqev (vusolimogene oderparepvec-wtpg), the oncolytic immunotherapy long known as RP1, in combination with nivolumab (Opdivo) for adults with unresectable advanced cutaneous melanoma that has progressed on an anti-PD-1 antibody-based regimen.
The decision transforms Replimune (NASDAQ: REPL) from a clinical-stage biotech into a commercial-stage company with its first marketed product, and ends a regulatory ordeal that had come to symbolize the strained relationship between drug developers and an FDA in the midst of unprecedented leadership churn.
Two Rejections and a Public Falling-Out
Replimune first filed its Biologics License Application in late 2024, backed by the Phase 1/2 IGNYTE trial and a breakthrough therapy designation. The FDA’s first Complete Response Letter arrived in July 2025, with the agency concluding that the single-arm study was not an adequate and well-controlled investigation and that its results could not be interpreted due to the heterogeneity of the enrolled population. No safety issues were raised, a detail that made the rejection all the more surprising to a company that believed it had aligned with the agency throughout development.
A resubmission was accepted in October 2025 under a Class II timeline, only for the FDA to issue a second CRL on the April 10, 2026 action date. This time Replimune did not hold back. CEO Sushil Patel said the company’s efforts had been “met with inconsistent communication and a fragmented and slow-moving regulatory process,” and asserted that the second rejection contradicted positions FDA staff had taken during a Type A meeting in September 2025.
The company was not alone. RP1 became a litmus test for an agency whose decision-making, amid deep staff cuts and a revolving door of senior officials, was increasingly described by industry as mercurial, with Moderna, uniQure, Regenxbio, Biohaven, Vanda Pharmaceuticals, and Capricor Therapeutics among the companies reporting shifting or contradictory feedback during the same period.
What Changed at the Agency
The turning point came in late May 2026, when Replimune announced that renewed dialogue with the FDA had produced alignment on a path forward, a development that followed the departures of CBER Director Vinay Prasad at the end of April and, weeks later, Commissioner Marty Makary, who had publicly defended the rejections. Shares jumped nearly 80% on the news, and the stock ultimately climbed more than 135% from its post-CRL lows as the third attempt took shape.
The FDA, for its part, signaled urgency. The June resubmission was classified as a complete Class 1 response, assigned an August 2, 2026 PDUFA date, and routed to the Cellular, Tissue, and Gene Therapies Advisory Committee in late July. On July 30, the panel voted 10–3 that the IGNYTE efficacy results were evaluable and clinically meaningful, overriding the concerns of FDA reviewers, who continued to question the trial’s design and the interpretability of RECIST-based responses in an intratumorally injected therapy. More than 30 public speakers, including patients treated with RP1, urged approval, and panelists in the majority argued the therapy should be available while the confirmatory Phase 3 trial reads out. Four days after the PDUFA date, the agency agreed.
The Data Behind the Approval
The label rests on IGNYTE, which enrolled 140 patients with advanced melanoma and confirmed progression on at least eight weeks of prior anti-PD-1-based therapy. In the FDA’s efficacy-evaluable population, 91 patients with at least one non-injected lesion, Tudriqev plus nivolumab produced an objective response rate of 24.2% and a median duration of response of 14.1 months, in a population that was 80% Stage IV and 54% PD-L1 negative. Broader analyses of the full cohort, published in the Journal of Clinical Oncology, reported a 33.6% objective response rate by independent central review, complete responses in 15% of patients, and a three-year overall survival rate of 47.8%, rising to 83.5% among responders.
Tudriqev, a genetically engineered herpes simplex virus type 1 expressing GM-CSF and a GALV-derived fusogenic glycoprotein, is injected directly into tumors every two weeks for eight consecutive doses, with nivolumab given intravenously beginning at week three. Adverse events in IGNYTE were predominantly grade 1–2 and transient, fatigue, pyrexia, chills, nausea, and injection-site reactions, with no common grade 4 or 5 events, though serious adverse reactions occurred in 35% of treated patients, and the label carries warnings for herpetic infection, accidental exposure of close contacts to the live virus, and injection-related visceral injury.
From Clinical-Stage to Commercial-Stage
Replimune has set a list price of $450,000 per course before rebates and discounts, and is launching with ReplimuneConnect Plus, a patient access and reimbursement support program. Commercial preparations had been underway ahead of the original April action date, and shares closed up nearly 9% at $12.86 on approval day.
The commercial question now is whether Tudriqev can succeed where the field’s only precedent stumbled. This is the first FDA approval of an oncolytic virus therapy since Amgen’s talimogene laherparepvec (T-VEC) in 2015, a product that never achieved meaningful commercial traction. Replimune’s bet is that a defined post-anti-PD-1 indication, roughly half of advanced melanoma patients ultimately fail or progress on checkpoint blockade, and response rates to continued anti-PD-1 therapy historically run in the single digits, gives Tudriqev a clearer clinical role than its predecessor ever had.
What’s Next
The approval is conditional. Continued authorization may hinge on the ongoing Phase 3 IGNYTE-3 trial, which randomizes approximately 400 patients to RP1 plus nivolumab against physician’s choice of therapy, nivolumab plus relatlimab, anti-PD-1 rechallenge, or single-agent chemotherapy, with overall survival as the primary endpoint and data expected in 2030. A negative readout would put the accelerated approval, and Replimune’s first franchise, at risk.
For the broader sector, the read-through is just as consequential. After two years in which biotechs publicly questioned whether the FDA’s feedback could be trusted, RP1’s reversal suggests the agency’s new leadership is willing to exercise flexibility for refractory populations with high unmet need, and to let advisory committees, clinicians, and patients tip the balance. Whether that posture holds, IGNYTE-3 will be the test case once again.
Read also Third Time at the Table: Why Replimune’s RP1 Deserves a Real Hearing in Post-PD-1 Melanoma
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Written by: Semiramida Nina Markosyan, Editor, OncoDaily Canada