Replimune's RP1 Melanoma Drug Gains New Life with FDA Resubmission Acceptance

In a surprising turn of events, Replimune announced on Monday that the U.S. Food and Drug Administration (FDA) has accepted a resubmission for RP1, its advanced melanoma drug candidate. This development comes just one month after the company had set low expectations for the drug's future, following a previous rejection by the regulatory agency.

FDA Reversal Breathes New Hope into RP1

RP1, also known as vusolimogene oderparepvec, is designed to be used in combination with Bristol Myers Squibb's checkpoint inhibitor Opdivo (nivolumab). The therapy is an engineered, proprietary strain of the herpes simplex virus that replicates in tumors and induces a heightened immune response.

The FDA's acceptance of the resubmission marks a significant shift from its earlier stance. In July, the agency rejected Replimune's initial biologics license application (BLA) for RP1, citing concerns about the adequacy of the Phase III IGNYTE trial. The complete response letter (CRL) indicated that the FDA did not consider the study an "adequate and well-controlled clinical investigation."

Replimune CEO Sushil Patel expressed satisfaction with the FDA's decision, stating, "We are pleased the agency has accepted the resubmission of our BLA for RP1. RP1 plus nivolumab offers a strong risk benefit profile where there are few options for patients with advanced melanoma, who have progressed on PD-1 based therapy."

Regulatory Path Forward and Market Response

The FDA has set a target action date of April 26, 2026, based on a Class II resubmission timeline. This news has had a dramatic impact on Replimune's stock, with shares soaring approximately 93% to $8.69 apiece as of Monday's publication.

BMO Capital Markets analysts noted, "Today's announcement comes as a change of tune at the FDA. We see a reversal of this sentiment in today's announcement with the company noting that the FDA has accepted Replimune's resubmission and is considering it a complete response."

The resubmission includes additional information, data, and analyses, which will be part of the BLA review. This development provides what BMO describes as a "potential path forward" for RP1, contrasting sharply with the uncertainty that followed the initial rejection.

Controversy and Expert Intervention

The rejection and subsequent acceptance of RP1's application have been marked by controversy within the regulatory process. In August, 22 scientists involved in designing and running the IGNYTE trial penned an open letter to the FDA, addressing issues outlined in the CRL and urging the agency to "re-review" Replimune's application.

Adding to the complexity of the situation, reports emerged of direct intervention by Richard Pazdur, director of the FDA's Oncology Center of Excellence (OCE) and acting director of the Office of Oncologic Diseases. An unnamed FDA official told STAT News that the Center for Biologics Evaluation and Research had "mishandled the RP1 review from the beginning," necessitating involvement from Pazdur and his team.

As the pharmaceutical industry watches closely, the fate of RP1 now hangs in the balance, with the potential to offer a new treatment option for patients with advanced melanoma who have progressed on PD-1 based therapy.