Replimune Group Inc. (NASDAQ:REPL) on Friday received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration for its Biologics License Application.

The application sought approval of RP1 in combination with nivolumab for advanced melanoma, challenging the agency's assessment of its data package.

The company argued that the dataset supporting its breakthrough therapy designation should have been sufficient for accelerated approval, pointing to results from the IGNYTE trial.

In that study, patients who had progressed on prior anti-PD-1 therapies showed a 34% response rate when treated with RP1 plus nivolumab, with a median duration of response of 24.8 months and a favorable safety profile.

Replimune Flags Review Inconsistencies

Replimune highlighted what it described as inconsistencies in the FDA's review process. According to the company, a new review team was assigned during the resubmission phase, replacing the original team that had engaged with the company earlier.

The company also noted that the new team did not meet with management during the review, despite outreach efforts. It further pointed to prior statements from a senior reviewer indicating that the clinical team had supported the evidence package, though leadership disagreed.

Disputes Over Trial Design And Data Interpretation

Replimune said the CRL contradicts earlier FDA feedback, particularly from a September 2025 Type A meeting.

At that time, the agency had not raised additional concerns about patient heterogeneity and acknowledged challenges in conducting randomized trials in this setting.

The company also submitted additional analyses, including data showing median progression-free survival of 30.6 months with RP1 plus nivolumab versus 4.4 months on prior therapies.

It claims the FDA did not respond to requests for feedback before accepting the resubmission.

Replimune Analysts Turn Bearish Following Regulatory Setback

HC Wainwright downgraded Replimmune from Buy to Sell. Analyst Robert Burns sees a significantly longer path for RP-1 to reach the market, if at all.

"It may take until late in this decade to furnish the agency with the data that it appears to be demanding. There can be no assurance that Replimune would be able to accomplish this. As such, the company is facing a significant crisis and may not be able to pivot successfully," Burns added.

Jefferies also downgraded Replimune from Buy to Hold and lowered the price forecast from $13 to $2.

Wedbush downgrades Replimune from Outperform to Neutral and lowers the price target from $19 to $2.

JP Morgan shifted its rating from Neutral to Underweight.

Leerink Partners downgraded Replimune from Outperform to Market Perform and lowered the price target from $11 to $2.

Cantor Fitzgerald also downgrades Replimune from Overweight to Neutral.

REPL Price Action: Replimune Group shares were down 63.97% at $1.71 at the time of publication on Monday. The stock is trading at a new 52-week low, according to Benzinga Pro data.

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