Key TakeawaysFDA issued a second complete response letter denying approval for Replimune’s RP1 melanoma immunotherapyThe treatment was under review for use with Bristol Myers Squibb’s (BMY) OpdivoRegulatory concerns focused on clinical trial design, not safety profileShares plummeted approximately 19% to $4.76, with trading paused twice due to extreme volatilityCurrent trading price sits significantly below the 52-week peak of $13.24Replimune (REPL) has encountered a second regulatory roadblock as the FDA maintains its position regarding the clinical trial methodology supporting the RP1 application.Replimune Group, Inc., REPLThe regulatory agency delivered a complete response letter rejecting vusolimogene oderparepvec (RP1) for combination therapy with Bristol Myers Squibb’s (BMY) Opdivo in treating advanced melanoma patients previously exposed to anti-PD-1 therapies.In correspondence directed to Kari Jeschke, Replimune’s senior vice president of regulatory affairs, the FDA confirmed that supplementary exploratory analyses of the study data failed to change its prior assessment. The RPL-001-16 clinical investigation was classified as inadequate and lacking proper controls.No safety flags were raised by the FDA — the primary obstacle centers on demonstrating sufficient efficacy.This marks the second time the application has been turned down. The initial rejection occurred in July 2025, following Vinay Prasad’s appointment as head of the FDA’s Center for Biologics Evaluation and Research by two months. The company resubmitted its Biologics License Application, which gained acceptance for regulatory review in October 2025.Shares of REPL experienced a sharp decline of roughly 19% to $4.76 following the announcement. Trading experienced two separate halts throughout the session as volatility thresholds were triggered. According to Dow Jones Market Data, this price level represents the stock’s lowest closing position since October.Compared to its 52-week high of $13.24, REPL now trades at a substantial discount.Understanding RP1RP1 represents a genetically modified variant of Herpes Simplex Virus type 1 — the identical virus responsible for cold sores. The company engineered it to selectively replicate within tumor cells, destroying them through cell lysis while simultaneously stimulating enhanced immune activity from the body’s white blood cells.This candidate serves as the flagship asset in Replimune’s RPx platform, dedicated to developing oncolytic immunotherapies targeting solid tumors.The organization maintains a market capitalization of approximately $393 million. Without positive earnings, the company reports no P/E ratio — a typical characteristic for clinical-stage biotechnology firms developing their product portfolios.Insider Trading Patterns and Company FundamentalsReplimune registers a GF Score of 40 out of 100, with profitability metrics scoring just 1 out of 10. The company’s financial strength receives a 6 out of 10 rating.During the most recent three-month period, company insiders offloaded $0.1 million in shares, while no insider purchases were documented.The stock currently trades at $4.76, representing a significant discount from the year’s peak of $13.24 achieved earlier.The post Replimune (REPL) Shares Plunge 19% Following Second FDA Rejection of RP1 Melanoma Treatment appeared first on Blockonomi.