Replimune’s resubmission for RP1 for melanoma comes amid the departures of FDA leaders in place at the time of the drug’s first two rejections, last summer and again in April.
Replimune will give its tumor destroyer RP1 another try, testing its regulatory luck for a third time after key changes in FDA leadership.
Following two previous rejections, the company will resubmit its biologics license application for the melanoma therapy “in the coming days,” according to a news release on Friday. Replimune is proposing RP1 in combination with Bristol Myers Squibb’s PD-1 blocker Opdivo for advanced melanoma with disease progression after prior PD-1 treatment.
“Third time’s the charm?” asked BMO Capital Markets analysts in a Friday note. “We see this as a positive, but remain cautious as we’re uncertain what has actually changed” at the FDA that could open up a different outcome for Replimune, they said, noting that RP1’s “third submission may reflect recent changes at FDA including departure of Commissioner [Marty] Makary.”
The FDA has indicated that it will treat Replimune’s resubmission as an “urgent matter” and prioritize its review, the biotech said.
The decision to refile comes after what Replimune CEO Sushil Patel called “collaborative dialogue” with the FDA “towards finding a meaningful path forward for RP1.” It is unclear what specific changes opened the door to the resubmission, but it comes after a series of high-level exits at the regulator.
At the start of the month, for instance, Vinay Prasad, former director of the Center for Biologics Evaluation and Research (CBER), left the FDA. Soon after, Makary stepped down as commissioner, ending what analysts at Capital Alpha called the “most damaging period in FDA history.”
It was under Prasad and Makary that Replimune suffered its second rejection for RP1, which the FDA dished out in April.
“Every accept or reject decision at the FDA, on my watch, has been the accept or reject recommendation of the primary review teams at the agency,” Makary said in an interview with CNBC earlier this month, responding to continued criticism over RP1’s rejection. “I stand by the scientists at FDA.”
RP1’s first rejection came in July 2025. While Makary and Prasad were already in their posts by this time, that decision was reportedly driven by former FDA oncology leader Richard Pazdur. Makary tapped the cancer stalwart in November to head the agency’s Center for Drug Evaluation and Research (CDER), but Pazdur retired just weeks after accepting the job.
He was succeeded in an interim capacity by Tracy Beth Høeg, who has also since been removed.
CBER is now led by Karim Mikhail, while CDER’s chief is Michael Davis. Both are acting directors and will serve until the FDA is able to find permanent replacements. Meanwhile, the agency’s top role is currently held by Kyle Diamantas, the FDA’s top food executive, also in an acting capacity.
