FDA Delays Approval of Replimune’s Melanoma Therapy Despite Promising Trial Results

For now, the FDA has denied approval today of a new melanoma treatment developed by Replimune. The company’s lead drug candidate, RP1 (vusolimogene oderparepvec), used alongside the immunotherapy drug Opdivo (nivolumab), was being reviewed as a treatment for patients with advanced melanoma.

In a Complete Response Letter (CRL) to the company, the FDA said it could not approve the treatment based on the current evidence. The agency cited problems with the design of the main clinical trial, called IGNYTE.

More specifically, the FDA said the trial did not meet the standard of being “adequate and well-controlled” and that the variety in the patient population made the results difficult to interpret. The FDA also raised concerns about how the company designed its future confirmatory study, especially regarding how much of the benefit came from RP1 versus Opdivo.

The FDA has rejected Replimune’s application for its experimental melanoma therapy RP1, citing concerns with the clinical trial’s design and data interpretation. © Evgeny—stock.adobe.com.

However, the FDA did not raise any concerns about the safety of the treatment.

According to the American Cancer Society, an estimated 104,960 new cases of melanoma will be diagnosed in 2025—about 60,550 in men and 44,410 in women—and approximately 8,430 people are expected to die from the disease, including 5,470 men and 2,960 women.

Replimune, which is based in Massachusetts and focuses on developing cancer treatments using engineered herpes viruses, said it will request a Type A meeting with the FDA to discuss next steps. These meetings typically take place within 30 days.

“We are surprised by this FDA decision and disappointed for advanced melanoma patients who have limited treatment options as highlighted by the granting of breakthrough status at the time we provided the IGNYTE primary data,” said Sushil Patel, Ph.D., CEO of Replimune, in a news release. “The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study. We strongly believe that RP1 in combination with nivolumab can bring substantial benefit to advanced melanoma patients.”

This setback comes shortly after researchers presented encouraging data from the IGNYTE trial at the 2025 American Society of Clinical Oncology (ASCO) meeting.

The trial tested RP1 together with Opdivo in patients with advanced melanoma who had stopped responding to earlier treatments. About one-third of the patients saw their tumors shrink by at least 30%, and in some cases, the tumors disappeared completely. The treatment seemed to help not just the injected tumors but also tumors in other parts of the body, as previously reported in Managed Healthcare Executive.

“These findings are very encouraging because melanoma is the fifth most common cancer for adults, and about half of all advanced melanoma cases cannot be managed with currently available immunotherapy treatments,” said Gino Kim In, M.D., a medical oncologist at Keck Medicine of USC and a lead investigator at one of the clinical trial sites, in a news release. “The survival rate of untreatable advanced melanoma is only a few years, so this new therapy offers hope to patients who may have run out of options.”

RP1 is part of a growing field of cancer treatments called oncolytic virus therapies. These use modified viruses that selectively infect and destroy cancer cells while also activating the body’s immune response.

One earlier therapy, Amgen’s Imlygic (talimogene laherparepvec), was approved in 2015 and is also based on a herpes virus. RP1 builds on this idea with extra modifications: it includes GM-CSF, a molecule that stimulates immune cells and a fusogenic protein designed to boost its ability to kill tumor cells and activate the immune system.

RP1 is injected directly into tumors. Once inside, the virus replicates and kills cancer cells while signaling the immune system to attack other tumors throughout the body. In the IGNYTE trial, patients received the RP1 and Opdivo combination every two weeks for up to eight cycles. Those who responded well continued on nivolumab alone for up to two years.

One-year survival among patients was over 75%, and most side effects were mild.

Before this disapproval, Replimune was enrolling patients in IGNYTE-3, a larger phase 3 trial that was planned to include more than 400 participants as of mid-July. The company has also been studying RP1 in other types of skin cancers, including Merkel cell carcinoma and basal cell carcinoma.

The FDA’s decision reflects how high the bar is for new cancer treatments to gain approval, especially when trial designs are complex. However, Replimune and its investigators believe the data show strong potential.