An FDA advisory committee voted 10-3 that trial results indicate Replimune's combination of vusolimogene oderparepvec (RP1) with nivolumab is effective for patients with advanced melanoma who have previously received an anti-PD-1-containing regimen.

The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee did not vote on whether the drug should be approved, but affirmed that the efficacy results from the IGNYTE trial were evaluable and clinically meaningful.

Melanoma is the fifth-most common cancer in the US, with some 112,000 cases and 8500 deaths a year. There are few alternatives for those who do not respond to a PD-1 therapy. 

Oncologists on the committee who voted affirmatively said the unmet medical need, plus response rates, drove their decision.

"There were tumors which shrunk, both the injected ones and the non-injected ones, that resulted in clinical benefit for patients that otherwise don't have any other options," said Hussein A. Tawbi, MD, PhD, professor of melanoma medical oncology at University of Texas MD Anderson Cancer Center, in Houston. 

The therapy should be available to patients even as clinicians await results of an ongoing phase 3 study, said Tawbi.

"The efficacy signal was substantial enough, durable, and fairly consistent across clinically relevant subgroups," said panelist David M. Miller, MD, PhD, director of the Center for Merkel Cell Carcinoma at Massachusetts General Hospital, Boston.

"I was also deeply affected by the testimony today," he added.

Other panelists mentioned the public comments as a motivating factor. Some 30 speakers — primarily individuals who have, or had melanoma, or cared for family members with the disease, along with many oncologists who took part in RP1 trials — spoke for 90 minutes. Those who had experience with RP1 said that it had extended their survival.

Potential for Stunning Reversal 

The FDA usually follows advisory panel recommendations, but it would be a potentially stunning reversal if the agency approves RP1.

FDA granted the drug breakthrough designation in November 2024 based on phase 2 data from IGNYTE and granted priority review in January 2025. But in July 2025, the agency issued a complete response letter, stating that IGNYTE was not adequate and well-controlled.

A few months later, Replimune submitted essentially the same data, according to the FDA. The agency rejected RP1 again in April 2026. After a new series of meetings with the FDA, Replimune submitted data again in June 2026, which led to the advisory panel meeting.

In briefing documents, and in remarks at the meeting, FDA officials acknowledged the unmet need for advanced melanoma patients. But officials also said that Replimune had ignored agency advice over years of meetings.

Sundeep Agrawal, MD, of the FDA's Oncology Center of Excellence, said at the meeting that the agency had done much to accommodate the company. But, he said, "FDA's flexibility does not extend to accepting unreliable efficacy data or waiving the requirement for substantial evidence of effectiveness."

Debate About Response Rate 

Among other issues, the FDA and Replimune differed on which trial patients should be considered a responder. Replimune included patients with directly-injected lesions, leading to an objective response rate of 33.6% (47 of 140 patients). FDA calculated an objective response rate of 15.7% (22 of 140 patients). Replimune also stated that the median duration of the overall response was 24.8 months, while FDA said it was 14.1 months.

The agency also said it was not possible to determine whether responses in patients were due to RP1 or nivolumab. 

Some panel members agreed with FDA officials and said it was not possible to evaluate the company's submitted results.

"There's just so much uncertainty," said Karla Ballman, PhD, a professor of biostatistics at the Mayo Clinic College of Medicine and Sciences. She said the overall response rate and duration of response could not reliably be calculated in a single-arm study like IGNYTE.

Most panelists, however, saw an efficacy signal.

The responses are "reliable enough in my perspective," said Tawbi.

Although the FDA said it identified several serious and potentially life-threatening adverse events in IGNYTE that may have been RP1-related, committee members said the combination's toxicity profile was preferable to current alternatives.

"The lack of major safety signals or concerns is appealing to me," said panelist Jorge A. Garcia, MD, MSC, chair of the division of solid tumor oncology at UH Seidman Cancer Center, in Cleveland.

"I think this agent works," Garcia said, adding that he went into oncology because "personally and professionally, I believe in hope." 

At the meeting's conclusion, Megha Kaushal, MD, MSc, acting deputy director of FDA's Office of Therapeutic Products, said the agency will carefully consider the committee's recommendations, the open public hearing, and the "totality of the scientific discussion" in weighing approval of RP1.

The FDA has said it would issue a decision by August 2. 

The experts cited in this article had no relevant disclosures. 

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.