Replimune announced on Apr. 10 that the United States Food and Drug Administration (FDA) has rejected its advanced melanoma drug, RP1, for the second time. The decision led to a nearly 20% drop in Replimune's stock.
The FDA's continued refusal to approve RP1, also known as vusolimogene oderparepvec, highlights ongoing debate about trial design and regulatory standards in cancer drug approvals. The rejection follows months of scrutiny after the agency's first denial in July 2025 and comes despite new analyses submitted by Replimune regarding the drug’s mechanism of action and patient outcomes compared to previous immunotherapy treatments.
According to the FDA’s Complete Response Letter published Friday, a different review team was assigned this time "to maintain objectivity and account for potential bias." Despite this measure, regulators found that data from Replimune were "insufficient to conclude substantial evidence of effectiveness" for treating unresectable advanced cutaneous melanoma when used with Bristol Myers Squibb’s Opdivo. The agency further wrote that it "would not recommend" seeking approval based on results from a single-arm study—a key issue given Replimune relied on such a trial design.
The use of alternative trial designs like single-arm studies has been controversial among biotech observers following this case. While recent FDA guidance supports innovative approaches including external controls, application appears inconsistent according to industry analysis. In its letter, the FDA stated its advice “has remained consistent as evidenced by our communications dating back to March 2021 and subsequent interactions.”
There is apparent disagreement between the company and regulators over communication throughout the process. Chief Executive Officer Sushil Patel said after the initial rejection: “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.”
Replimune had sought accelerated approval for RP1 but is now conducting a randomized Phase 3 trial with Opdivo which is expected to be completed by January 2029.
Analysts have viewed this case as an indicator of future regulatory trends at FDA affecting both companies and patients awaiting new therapies.
