FDA Rejects Replimune's Melanoma Drug, Sending Shares Plummeting

Replimune's bid for accelerated approval of its melanoma drug candidate RP1 has been rejected by the U.S. Food and Drug Administration (FDA), dealing a significant blow to the biotech company and its investors. The news, announced on July 22, 2025, sent Replimune's stock price crashing by 76% in premarket trading, dropping to below $3 per share.

FDA Concerns and Complete Response Letter

The FDA's decision came in the form of a Complete Response Letter (CRL), citing several issues with Replimune's submission. According to the agency, the phase 1/2 Ignyte trial, which tested RP1 in combination with Bristol Myers Squibb's checkpoint inhibitor Opdivo, was not considered "an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness."

The FDA highlighted concerns about the heterogeneity of the patient population in the study, stating that the trial "cannot be adequately interpreted" due to this factor. The agency also raised issues with the design of Replimune's proposed phase 3 confirmatory trial, including aspects related to "contribution of components."

Replimune's Response and Future Plans

Replimune's CEO, Sushil Patel, Ph.D., expressed surprise and disappointment at the FDA's ruling. "The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study," Patel stated.

The company plans to request a meeting with the FDA and engage in urgent interactions to find a path forward. However, Replimune warned that without timely accelerated approval of RP1, the development of the drug candidate for advanced cancer patients with limited options may not be viable.

Financial Implications and Industry Context

The rejection of RP1 adds to a growing list of assets receiving complete response letters from the FDA in recent months. This trend has raised concerns within the pharmaceutical industry about the agency's evolving approach to drug approvals.

Replimune reported $483.8 million in cash reserves as of March 2025. The company had previously estimated that the RP1 confirmatory trial would "take a couple of years to complete enrollment given the study population and size of the study."

As the biotech sector grapples with increased regulatory scrutiny, Replimune's setback serves as a stark reminder of the challenges facing drug developers in the current landscape.