What RP1 Was Supposed to Do

Replimune’s RP1 is an oncolytic virus therapy aimed at treating advanced melanoma by activating the immune system in combination with Bristol Myers Squibb’s Opdivo. It was given breakthrough therapy and priority review status after early results from the Ignyte trial, where around 33% of patients saw their tumors shrink, even after failing PD-1 inhibitors. The responses were durable, but the FDA still rejected the application for accelerated approval in July 2025.

Why the FDA Said “No”

The agency sent a Complete Response Letter highlighting major concerns with the supporting data. According to Replimune, the FDA said the Ignyte trial was not seen as an adequate and well-controlled clinical study that could prove the drug’s effectiveness. They also raised concerns about how the trial's diverse patient population made the results hard to interpret. On top of that, the FDA flagged unresolved issues in the design of Replimune’s planned Phase III confirmatory trial.

Internal FDA Showdown: Pazdur vs. CBER (and No Prasad Involvement)

The review exposed some sharp internal divides at the FDA. Sources said Richard Pazdur, the agency’s top oncology official, stepped in during the final stages and pushed for a rejection. In contrast, teams at the Center for Biologics Evaluation and Research, which normally handles biologic drug approvals like RP1, were reportedly more open to the application.

Despite speculation, Vinay Prasad had no real role in the outcome. He deferred to Pazdur's judgment. The broader issue was a wave of leadership changes and internal friction that left Replimune caught in the middle.

How Wall Street and Replimune Reacted

Investors were caught off guard. Replimune’s stock crashed by 75 to 77 percent, falling below $3 for the first time. CEO Sushil Patel called the decision “surprising and disappointing,” arguing that the FDA raised new concerns that hadn’t been mentioned during earlier review cycles.

What’s Next for Replimune and Patients

The company has formally requested a Type A meeting, which the FDA is required to schedule within 30 days. Replimune still believes RP1 can help patients with limited treatment options. Moving forward, they may revise the trial design, narrow down who qualifies, or include a control group to address the FDA’s concerns.

It’s a serious setback, but not a final blow.

What This Really Means

In biotech, how you present data matters just as much as the results themselves. A single-arm, midstage trial can struggle to gain traction, especially when the patient group is highly varied and the agency is asking for tighter evidence. The RP1 case reveals just how tough the FDA’s path can be for cell and gene therapy developers, especially with internal power struggles and leadership shifts in play.

If Replimune can tighten its approach and deliver stronger evidence, accelerated approval could still be on the table. But the takeaway is clear: at the FDA, internal politics can shape the outcome just as much as science.