The upcoming FDA decision for Replimune’s advanced melanoma drug could be a litmus test for the agency’s future regulatory decision-making, analysts say, with implications stretching well beyond one company.
Last month, the FDA revealed that embattled Center for Biologics Evaluation and Research chief Vinay Prasad would step down from his role at the end of April. This is just the latest in an unprecedented streak of agency departures during the past year, including that of long-time chief cancer regulator and short-term Center for Drug Evaluation and Research head Richard Pazdur. Both men were thought to have played a part in the rejection of Replimune’s advanced melanoma drug candidate. This week, that asset will get another chance.
While Replimune and the advanced melanoma community wait at the edge of their seats for the FDA’s decision on the drug, called RP1, the outcome could affect the biopharma industry more broadly. The agency’s action on this filing is being regarded as a barometer of the FDA’s regulatory decision-making, Cantor Fitzgerald analyst Li Watsek told BioSpace.
“I think a lot of folks are looking at Replimune’s PDUFA date as a first indicator of how the FDA is going to act going forward,” Watsek told BioSpace. “There’s a lot of chatter about political pressure and the way that FDA leadership has handled approvals.”
Last July, Replimune, which is developing novel oncolytic immunotherapies for difficult-to-treat cancers, was hit with an unexpected complete response letter (CRL) for RP1. Two weeks later, it was revealed that Pazdur had objected to its approval, overruling the overall consensus at CBER. Prasad—whom analysts originally suspected to be behind the rejection—ultimately deferred to Pazdur.
Last October, following protests from researchers on RP1’s trials, the FDA accepted Replimune’s resubmitted biologics license application for the drug.
Replimune is not alone in being stymied by intervention from senior FDA leaders. Prasad reportedly played a role in rejections for Capricor Therapeutics’ Duchenne muscular dystrophy cardiomyopathy drug deramiocel, also in July 2025, and more recently for Disc Medicine’s rare blood disease drug bitopertin.
A Surprise CRL
RP1’s initial rejection was controversial because the therapy was fully expected to be approved, according to Robert Driscoll, senior vice president of equity research at Wedbush Securities.
It came as a surprise to Replimune CEO Sushil Patel who noted in a statement at the time that the issues highlighted in the CRL were not raised by the FDA during mid- and late-cycle reviews.
The drug, in combination with Bristol Myers Squibb’s PD-1 blockbuster Opdivo led to a 32.9% overall response rate, with a complete response rate of 15% in the Phase 2 IGNYTE trial, meeting its primary endpoint.
The overall data were “very convincing,” Driscoll told BioSpace, adding that previous studies indicated a significantly lower response rate of just 6–7% for PD-1s alone in the same patient population.
However, the FDA suggested in the CRL that the higher response rate could not be adequately interpreted due to the heterogeneity of the trial patient population. The agency attributed this to varying types of prior therapy received by patients and duration of treatment, among other factors.
Two weeks after the rejection, 22 experts involved in the design and execution of IGNYTE penned an open letter in which they contended that that such heterogeneity was representative of a real-world treatment scenario. To address this objection, Replimune would need to run a control arm with Opdivo monotherapy, they said. However, this would be “impractical, unacceptable and borders on the unethical.”
While advocacy for a certain treatment is not unheard of in the rare disease space, Watsek said the open letter and strong support for RP1 is “quite remarkable.” It is particularly uncommon for physicians in oncology to take such action, she added.
Given all these factors, the initial rejection appears to be due to the decision-making of either Pazdur or Prasad, either alone or in combination, Driscoll said, and possibly related to the regulators’ objections to single-arm studies that do not include a control.
A 50-50 Shot at Approval
Replimune has a lot riding on the upcoming decision, slated to be delivered by April 10. RP1 is the company’s lead asset and, if approved, could generate peak sales of $800 million annually, according to Watsek.
If RP1 is not approved, the company has indicated it may discontinue development of the asset and focus on other pipeline treatments, Driscoll added. Replimune would then need to raise enough capital to advance other assets through the clinic, he said.
A type A meeting with the FDA in September 2025 failed to yield a clear path forward for RP1, according to the biotech. A month later, however, Replimune resubmitted its application. The company did not reveal what prompted this change; nevertheless, Replimune stated in a press release that the FDA indicated that it considered the resubmission to be “a complete response” to the CRL.
With the uncertainty around the FDA, that won’t give investors a lot of comfort that this is going to be a slam dunk.
As such, analyst sentiment around the reapplication is reasonably positive, Driscoll noted. Over the past few months, Replimune’s stock has been trading between $7 and $9, down from the highs of $12 prior to the rejection last July but substantially higher than the $3 it fell to on the release of the news. This reflects the idea that RP1 has a 50-50 shot at approval, Driscoll said. Wedbush views the odds more favorably than the broader market, as Driscoll predicted a 60–70% likelihood of success.
Looking to a ‘Post-Prasad’ Future
The imminent departure of Prasad—as well as the previous resignation of Pazdur—has heightened expectations for RP1’s approval, Watsek said, as both figures have been presumed to be involved in the “opposition” to the drug. Despite this, there is a lot of uncertainty over how the FDA will operate “post-Prasad,” she said. In addition, Prasad will remain head of CBER until the end of April, though it is unknown how active he will be, Watsek added.
“Even though there are good reasons to be hopeful, with the physician group having played a pretty visible and vocal role in protesting the CRL decision, there is still a lot of bearish sentiment,” she continued. “With the uncertainty around the FDA, that won’t give investors a lot of comfort that this is going to be a slam dunk.”
More broadly, Driscoll said, the biotech industry needs someone who is able to “steady the ship” to step into Prasad’s soon-to-be-vacated leadership position.
“We need someone to come in that allows biotechs to be more confident in how regulatory decisions are being made,” he said. “Regulatory decisions affect years of drug development and trial design, so we’d love to see some stability.”
