Replimune Caught in FDA Crossfire as Health Secretary Distances Himself from RP1 Rejection

FDA Commissioner Makary defends RP1 rejection as Health Secretary Kennedy distances himself, leaving Replimune's melanoma therapy in regulatory limbo and financial jeopardy.

The battle over Replimune's melanoma therapy RP1 has escalated into a political firestorm, with FDA Commissioner Marty Makary and Health Secretary Robert F. Kennedy Jr. offering sharply contrasting positions on the agency's second rejection of the drug. For the struggling biotech, the mixed signals from Washington are doing little to ease the pressure.

Makary went on the offensive this week, dismissing Replimune's criticism of the FDA as corporate spin. In a pointed interview, he insisted the agency had followed the science and accused the company of orchestrating a public relations campaign to pressure regulators. "I work for the American people," Makary said, standing firmly behind his scientists' decision to reject RP1 for a second time in less than a year.

But just a day later, Kennedy struck a markedly different tone. Testifying before the Senate on Wednesday, the Health Secretary distanced himself from the FDA's Complete Response Letter, stating he had no involvement in the decision. The disconnect between the two top health officials underscores the regulatory chaos enveloping Replimune's path forward.

At the heart of the dispute lies the IGNYTE study, a single-arm trial that formed the basis of Replimune's approval application for RP1 combined with Nivolumab in advanced melanoma patients who had failed prior anti-PD-1 therapy. The company reported an overall response rate of roughly 33.6%, but the FDA has consistently demanded randomized, controlled data to prove systemic anti-tumor activity. Replimune pressed ahead without meeting that requirement, and the agency rejected the application twice within 12 months.

The fallout has been severe. Replimune is slashing jobs and dramatically scaling back its U.S. manufacturing capacity in an effort to conserve cash. With a market capitalization hovering around $208 million, the company lacks the financial runway for lengthy new trials. Management has warned that without a swift accelerated approval pathway, the RP1 program may no longer be viable.

The company's stock has tumbled roughly 14.7% in recent sessions, trading near its 52-week low. Investors are pricing in the growing risk of dilutive capital raises as uncertainty drags on.

A so-called "Type A" meeting with the FDA is now the next critical milestone, where Replimune hopes to clarify exactly what the agency requires. The planned IGNYTE-3 confirmatory study was supposed to serve as the path forward, but agreement on its design has yet to be reached.

Makary's own position is increasingly precarious. With congressional elections approaching, the FDA faces mounting pressure from industry and the White House. Speculation about leadership reshuffling is adding to sector-wide unease. The Commissioner pushed back against accusations of political favoritism, insisting that drugs that work will get approved.

For Replimune, the clock is ticking. Without randomized data, U.S. market access remains a distant prospect, and the company's survival hinges on whether it can craft a regulatory strategy that satisfies both the FDA's scientific demands and its own financial constraints.