FDA hands another rejection to Replimune's melanoma therapy

Replimune has had its advanced melanoma treatment RP1 turned down by the FDA for a second time, a decision that has led the company to accuse the agency of inconsistencies in its review of the drug.

The biotech has been trying to get herpes simplex virus-based RP1 (vusolimogene oderparepvec) approved as a combination therapy with Bristol Myers Squibb's PD-1 inhibitor Opdivo (nivolumab) for patients with advanced melanoma who have progressed on anti-PD-1 treatment.

The FDA's complete response letter (PDF) notes that the regulator appointed a new team for the second review of RP1 to "maintain objectivity and account for potential bias" in the first, which led to a CRL being sent to Replimune in July 2025. The company, however, has accused it of "inconsistent communication and a fragmented and slow-moving regulatory process, which clearly puts US innovation at risk."

The company added that the decision goes against the opinion of "the country's foremost melanoma specialists" and the pleas of melanoma patients, and also claimed that the first review team had suggested RP1 was approvable, but was overruled by leadership at the agency.

The marketing application – seeking accelerated approval – is based on the results of the IGNYTE trial, which showed patients with confirmed progression on an anti-PD-1-based regimen who received RP1 plus nivolumab had a 34% response rate with a median duration of 24.8 months.

The latest CRL says that the new review team unanimously concluded that the IGNYTE results do not allow the effect of RP1 to be distinguished from Opdivo in the treatment regimen.

At the same time, it also had concerns about the size and make-up of the patient population enrolled in the study – although, Replimune asserts filing based on this dataset was agreed in 2021 and reaffirmed at a meeting last September– along with "uncertainty" in various clinical measures, including response assessments.

"It is deeply disappointing that the FDA has not exercised regulatory flexibility to meet patients' needs, given the data supporting strong efficacy and the favourable safety profile," said Sushil Patel, chief executive of the Woburn, Massachusetts-based biotech, who noted that approximately 8,500 Americans with advanced melanoma die every year.

"As we previously communicated, without timely accelerated approval, the development of RP1 will not be viable," he added.

"We are devastated for our committed employees who have worked tirelessly for patients, but at this point, we have no choice but to eliminate jobs, including substantially scaling back our US-based manufacturing operations. A treatment desperately needed by patients will not be available. Not because the medicine failed. Because the system did."

Shares in Replimune fell from just shy of $6 to a little over $2 after the outcome of the FDA's review was announced.