Dive Brief:
- Advisers to the Food and Drug Administration on Thursday voted in favor of an experimental melanoma treatment developed by Replimune, swatting away arguments by agency scientists that the company didn’t clearly show the treatment worked and that a survival analysis that it presented wasn’t “interpretable.”
- By a 10-3 vote, panelists concluded that the efficacy results from Replimune’s key study were “evaluable and clinically meaningful.” Their decision heightens the chance that the FDA will finally approve that treatment, “RP1,” after twice turning it back.
- The FDA is set to decide whether to approve RP1 by Aug. 2. Were the agency to spurn RP1 once again, the company would have to wait for results from a confirmatory trial — expected in late 2027 — before making a new submission.
Dive Insight:
Replimune wants the FDA to approve RP1 to help people who’ve seen their melanoma progress after getting a commonly used cancer immunotherapy like Merck & Co.’s Keytruda or Bristol Myers Squibb’s Opdivo. Response rates among those patients are particulary poor, and treatment options are limited. Replimune is hoping a combination of RP1 and Opdivo could change that.
The drug’s future has been closely watched, as Replimune was one of many companies charging the Marty Makary-led FDA with backtracking on previous agreements. It previously claimed, for instance, that an earlier review team thought the company had provided “adequate evidence” to prove RP1’s benefits. And its latest resubmission reportedly came after the White House intervened.
The trial it is using to support approval didn’t use a control arm, though. And the study mainly measured whether patients’ tumors shrunk or disappeared. Replimune found that about one-third saw some level of tumor response, and 15% went into complete remission. A survival analysis it conducted suggested that people who responded to RP1 lived significantly longer than those who didn’t.
To FDA scientists, Replimune’s findings fell short of definitive proof. In briefing documents filed ahead of the meeting, agency staff contended that the way Replimune designed its trial and evaluated responses made it difficult to distinguish the impact of RP1 — which is injected directly into a tumor — from those of Opdivo, a systemic therapy.
Those questions, in turn, rendered the survival data Replimune compiled and that compared “responders” to “non-responders” unreliable, FDA reviewers wrote.
The agency's arguments swayed at least some of the experts on the committee.
"I just don't even understand the data. I don't know what the response rate is. I don't know what to compare it to. We know that the chance of this being wrong, I think, is high," said Paul Chapman, the chief medical research officer of Weill-Cornell's Meyer Cancer Center, who voted against RP1.
Still, many study investigators have come to Replimune’s defense. And at a public hearing during the meeting, around 30 people claimed they’d benefited from treatment with RP1 were hoping for a chance to get it.
The majority of panelists challenged the FDA, too, arguing that, despite the flaws in Replimune’s trial, the results were meaningful enough in a particularly tough-to-treat patient group and displayed RP1’s impact. Those voting in favor of the therapy pointed to those factors, as well as the fact that the ongoing confirmatory study could quickly provide definitive answers on RP1’s benefits — and help people in the meantime.
"In my mind, this should be a therapy that's available to patients in the short term until the Phase 3 trial reads out," said Hussein Tawbi, a melanoma specialist at MD Anderson Cancer Center.
“Overall there is some signal there, and we should follow that signal,” added Jorge Garcia, chairman of the UH Seidman Cancer Center in Cleveland.
