FDA Cancer Regulator's Intervention Leads to Rejection of Replimmune's Melanoma Drug

In a surprising turn of events, Replimmune's advanced melanoma drug, RP1, has been rejected by the U.S. Food and Drug Administration (FDA) following an unexpected intervention by the agency's top cancer regulator. This decision has sent shockwaves through the pharmaceutical industry and caused significant financial repercussions for the company.

Unexpected Rejection and Stock Plunge

Two weeks ago, Replimmune received a complete response letter (CRL) from the FDA for RP1, a herpes virus-based immunotherapy designed to induce an immune response against tumors. The drug was being tested in combination with Bristol Myers Squibb's immunotherapy, Opdivo.

The rejection came as a shock to many, including Replimmune CEO Sushil Patel, who stated, "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."

The market reaction was swift and severe. Replimmune's stock crashed 75% immediately following the rejection and plummeted another 30% on Monday morning after the market opened, reflecting investor concerns about the company's future prospects.

FDA Internal Conflict and Intervention

Recent reporting from multiple outlets, including Endpoints News and STAT News, has revealed that the rejection was the result 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 within the Center for Drug Evaluation and Research (CDER).

According to anonymous FDA officials, Pazdur opposed the consensus opinion of staff at the Center for Biologics Evaluation and Research (CBER), where RP1 was under review. One FDA official told STAT, "This was Rick Pazdur's doing. I didn't agree with all the decisions made here by Vinay [Prasad], but he had little to do with this one."

The intervention appears to have been prompted by concerns over the handling of the review by CBER. Pazdur and his team at OCE were reportedly troubled by the design of the trials supporting RP1, arguing that the drug's tumor-killing effect could not be separated from the effect elicited by Opdivo.

Regulatory Implications and Industry Response

This incident has raised questions about the coordination between different FDA centers and the potential for last-minute interventions in the drug approval process. The rejection of RP1 came after a debate at a conference in early July, attended by both Pazdur and then-CBER director Vinay Prasad. While the consensus from the CBER side was that RP1 should be approved, Pazdur was in opposition. Ultimately, Prasad deferred to Pazdur's judgment.

The pharmaceutical industry is closely watching the fallout from this decision, as it may have implications for future drug development strategies and regulatory interactions. Replimmune has announced its intention to request a follow-up meeting with the FDA to understand how to move forward with RP1's development.

As the dust settles on this unexpected rejection, the industry awaits further clarification on the FDA's decision-making process and the potential impact on future cancer drug approvals.