FDA's Surprise Rejection of Replimmune's Melanoma Treatment Sends Shockwaves Through Pharma Industry

In a move that caught both industry analysts and the company off guard, the U.S. Food and Drug Administration (FDA) has issued a complete response letter rejecting Replimmune's viral treatment RP1 for advanced melanomas. The decision, announced on Tuesday, sent Replimmune's stock plummeting by 75% and raised questions about the potential impact of new FDA leadership on drug approvals.

FDA Rejects RP1, Citing Inadequate Clinical Investigation

Replimmune's biologics license application (BLA) for RP1, also known as vusolimogene oderparepvec, was supported by data from the Phase III IGNYTE trial. The study tested RP1 both as a monotherapy and in combination with Bristol Myers Squibb's checkpoint inhibitor Opdivo. However, the FDA's complete response letter indicated that the agency did not consider IGNYTE an "adequate and well-controlled clinical investigation," according to Replimmune's statement.

The rejection came as a surprise to Replimmune, with CEO Sushil Patel noting, "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."

New FDA Leadership May Signal Shift in Approval Standards

Analysts at BMO Capital Markets have pointed to recent changes in FDA leadership as a potential factor in the agency's decision. Of particular note is the appointment of Vinay Prasad as the new director of the Center for Biologics Evaluation and Research (CBER).

"We could see what reads as a final hour shake up, associated with a new FDA and head of CBER (Vinay Prasad), drive softness across the broader sector today," BMO analysts wrote in an investor's note. "Prasad has previously been critical of the approvability of uncontrolled data, and today we see that opinion underscored."

The BLA for RP1 was accepted with priority review on January 21, just one day into President Donald Trump's second term in office and while CBER was still under the leadership of Peter Marks, Prasad's predecessor. This timing has led to speculation about a potential shift in the FDA's approach to drug approvals under the new administration.

Implications for Replimmune and the Broader Oncology Field

RP1 is an engineered, proprietary strain of the herpes simplex virus designed to replicate in tumors and induce a heightened immune response. This mechanism of action is similar to Amgen's Imlygic, another drug that uses the herpes simplex virus to target melanoma cells.

The rejection of RP1 not only impacts Replimmune's advanced melanoma program but also raises questions about the company's ongoing studies of the treatment in non-melanoma skin cancers and for patients with skin cancer who have received organ transplants.

Replimmune has requested a follow-up meeting with the FDA and expects the request to be granted within 30 days. The outcome of this meeting could provide crucial insights into the agency's current stance on viral immunotherapies and the level of clinical evidence required for approval in oncology.

As the pharmaceutical industry digests this unexpected setback, many will be watching closely to see if this decision signals a broader shift in the FDA's approach to evaluating cancer treatments, particularly those based on novel mechanisms of action.