Key HighlightsFDA has now rejected Replimune’s melanoma immunotherapy RP1 on two separate occasionsThe drug was under consideration for use with Bristol Myers Squibb’s (BMY) Opdivo therapyRegulators maintained their position that the clinical trial lacked “adequate and well-controlled” standardsShares of REPL plummeted approximately 19% to $4.76, with trading paused twice for volatilityCurrent price sits significantly under the stock’s 52-week peak of $13.24Replimune’s (REPL) experimental melanoma treatment RP1 has encountered its second regulatory roadblock from the FDA, as the agency maintains its position regarding inadequacies in the clinical trial framework supporting the drug’s approval request.Replimune Group, Inc., REPLThe regulatory body delivered a complete response letter rejecting RP1, scientifically designated as vusolimogene oderparepvec, for combination therapy with Bristol Myers Squibb’s (BMY) Opdivo in treating advanced melanoma patients with prior anti-PD-1 therapy exposure.In correspondence addressed to Kari Jeschke, Replimune’s senior VP of regulatory affairs, FDA officials stated that supplementary exploratory data analyses failed to modify their previous determination. The agency concluded that the RPL-001-16 trial did not meet standards as an adequate and well-controlled clinical study.The FDA expressed no reservations regarding the drug’s safety profile — the core issue centers on insufficient efficacy demonstration.This marks the second regulatory denial. The initial rejection occurred in July 2025, approximately two months following Vinay Prasad’s appointment as head of the FDA’s Center for Biologics Evaluation and Research. Following this setback, Replimune resubmitted its Biologics License Application, gaining acceptance for review in October 2025.REPL shares declined roughly 19% to $4.76 following the announcement. Volatility circuit breakers triggered two separate trading halts during the session. According to Dow Jones Market Data, this price movement positions the stock toward its weakest close since October.The current valuation represents a substantial decline from the 52-week high of $13.24.Understanding RP1’s MechanismRP1 represents a genetically modified variant of Herpes Simplex Virus type 1 — the viral agent responsible for cold sores. Replimune’s engineering enables the virus to replicate exclusively within cancerous cells, leading to their destruction while simultaneously enhancing the immune system’s response through increased white blood cell activity.This therapeutic candidate serves as the flagship asset within Replimune’s RPx platform, which concentrates on developing oncolytic immunotherapies targeting solid tumors.The biotech company currently maintains a market capitalization of approximately $393 million. Without a P/E ratio due to negative earnings — typical for clinical-stage biotechnology companies developing their product pipelines.Internal Trading and Corporate FinancesReplimune’s GF Score registers at 40 out of 100, with profitability metrics scoring merely 1 out of 10. The company’s financial strength earns a 6 out of 10 rating.During the most recent three-month period, company insiders divested $0.1 million in shares, with zero purchases documented.Shares currently trade at $4.76, representing a significant discount from the year’s peak of $13.24 reached earlier.The post Replimune (REPL) Stock Plunges 19% Following Second FDA Rejection of Melanoma Treatment appeared first on Blockonomi.