Replimune wins FDA approval for Tudriqev in advanced melanoma after two previous rejections

Replimune has secured a long-awaited FDA approval for its melanoma therapy Tudriqev, marking a major reversal for a drug that had previously been rejected twice by U.S. regulators.

The FDA has granted accelerated approval to Tudriqev (vusolimogene oderparepvec), an engineered viral immunotherapy, for use in combination with Bristol Myers Squibb’s Opdivo (nivolumab). The treatment is intended for adults with unresectable advanced cutaneous melanoma whose disease has progressed following previous anti-PD-1 therapy.

The decision is based on findings from the Phase 1/2 Ignyte trial. Among 91 patients evaluable for efficacy, the Tudriqev-Opdivo combination produced an objective response rate of 24.2%, with responses lasting a median of 14.1 months.

The approval represents a significant turnaround for Massachusetts-based Replimune. Tudriqev, previously known as RP1, had faced two high-profile FDA rejections, with regulators questioning whether the available clinical data were sufficient to establish the drug’s effectiveness.

The regulatory dispute had also attracted attention beyond the company and the FDA. Former FDA Commissioner Marty Makary, M.D., publicly defended the agency’s previous decisions, while The Wall Street Journal’s editorial board cited the Replimune case in criticism of his leadership.

The latest decision followed an FDA advisory committee meeting in which external experts voted 10-3 in favor of Tudriqev’s overall profile. The vote came despite concerns from FDA reviewers about the design and interpretation of the clinical data.

One of the agency’s key concerns was the lack of a comparator arm in the trial. Without a control group, reviewers argued that it was difficult to determine how much of the observed benefit came specifically from Tudriqev rather than Opdivo. Regulators also questioned the treatment’s potential systemic effect because Tudriqev is administered directly into tumors.

FDA advisors acknowledged some of these limitations but ultimately concluded that the available evidence was strong enough to support approval. Even when patients who lacked sufficient tumor lesions for evaluating systemic response were excluded, the observed response rate remained well above historical outcomes for this patient population.

For Replimune CEO Sushil Patel, Ph.D., the approval represents the culmination of years of development work.

“This is a transformative moment for Replimune, marking years of pioneering research to bring Tudriqev to patients desperately in need of new treatment options for advanced melanoma,” Patel said in an Aug. 6 statement. He also thanked the FDA for recognizing the urgency of making the treatment available to patients.

However, the approval does not mark the end of the regulatory process.

Because Tudriqev received accelerated approval based on surrogate endpoints, Replimune must conduct a confirmatory trial demonstrating the therapy’s clinical benefit. The company is currently relying on the ongoing Phase 3 Ignyte-3 study for this requirement.

Ignyte-3 is comparing the Tudriqev-Opdivo combination with physician’s choice of therapy. The trial has enrolled roughly one-third of its planned participants, with results for the primary overall-survival endpoint expected in 2030, according to Replimune management during an investor call on Thursday.

Those randomized overall-survival results will also be important for the company's plans outside the U.S. Analysts at Leerink noted that Replimune will need the data to support regulatory approvals in international markets.

In the meantime, analysts expect the newly approved combination to generate strong interest among physicians and patients. Leerink Partners wrote in an Aug. 3 note that the regimen could see “strong demand” because of its relatively straightforward access and favorable safety profile. Most treatment-related adverse events reported with the combination have so far been Grade 1 or 2 and temporary.

Tudriqev could also offer a less complicated treatment experience than another option available to patients with cutaneous melanoma following anti-PD-1 therapy: Iovance Biotherapeutics’ Amtagvi.

Amtagvi, a cell therapy, involves a significantly more complex treatment process, including logistical challenges and the possibility of substantial side effects associated with different components of the therapy.

Replimune’s chief medical officer, Kostas Xynos, M.D., Ph.D., highlighted the practical differences during Thursday’s investor call.

“Tudriqev is an off-the-shelf treatment, practically for everyday clinical practice, that minimizes logistical complexity and treatment delays and ensures that patients with aggressive disease receive immediate care,” Xynos said.

For Replimune, the FDA decision therefore represents both a major commercial opportunity and the beginning of another important test: proving that the promising response data seen so far translate into a meaningful survival benefit.