An FDA advisory committee voted 10 to 3 in favor of approving Replimune’s cancer immunotherapy RP1 for advanced melanoma on July 30, despite significant concerns about the trial design and the overall efficacy of the drug. The therapy, known as vusolimogene oderparepvec or RP1, was tested in combination with Bristol Myers Squibb’s PD-1 checkpoint inhibitor Opdivo.
The vote addressed whether the registrational trial for RP1 and Opdivo was “evaluable and clinically meaningful.” While the FDA is not required to follow its advisory committees’ recommendations, it often does. An official decision on approval is expected by August 2.
RP1 has previously been rejected twice by the FDA. The main challenges for regulators stemmed from difficulties interpreting data from a Phase 1/2 IGNYTE study that measured anti-cancer effects based on tumor size. Several committee members acknowledged efficacy signals but noted that criteria such as response evaluation criteria in solid tumors (RECIST) needed further clarification for future decisions. Diane Aronson, a patient representative who voted against approval, said, “The science of the study did trouble me as far as the results, and the RECIST criteria is confounding… Hope is important, but reality weighed into my vote.” Lawrence Schwartz of Memorial Sloan Kettering Cancer Center called it “messy data,” but ultimately supported approval.
The back-and-forth between Replimune and the FDA began in 2021 when questions were raised about whether RP1 alone or its combination with Opdivo drove responses seen in trials. Sundeep Agrawal from the FDA oncology center said at Thursday’s meeting that survival data presented by Replimune showed nearly half of treated patients alive at three years but found overall response rates difficult to interpret: “Contribution of effect and the need for each product has not been demonstrated… Accelerated approval and traditional approval both require demonstration of substantial evidence of effectiveness derived from adequate and well-controlled trials.”
Despite these reservations, some experts argued for new approaches to evaluating cancer therapies. Jorge Garcia from University Hospitals Seidman Cancer Center described a “very imperfect endpoint,” while Michael Wong from Roswell Park Comprehensive Cancer Institute said, “My co-investigators and I are seeing patient responses to therapy that we have never seen before… In each of these situations, we have collectively had to reassess conventions and create new methodologies—we are at the same place now with this drug.”
Public comments during the meeting unanimously supported RP1’s approval. Sydney Morgan, diagnosed with stage 4 melanoma, told committee members, “There is plenty of data out on Opdivo, and if RP1 can augment its effectiveness for some people, that alone should be enough of an argument for approval… Currently there is no other new treatment for me to try.”
