Replimune Group received a second complete response letter (CRL) from the U.S. FDA for its immunotherapy vusolimogene oderparepvec in advanced melanoma, with the decision tied to an April 10 PDUFA date. The additional CRL underscores continued regulatory friction for an oncolytic therapy program that has been aiming to secure approval in a defined melanoma patient population. Shares fell more than 19% on the update. For sponsors and investors, the letter heightens attention on what FDA is requesting—typically additional analyses, trial data sufficiency, or manufacturing and clinical protocol clarifications—before a resubmission can move forward. The CRL also adds pressure to the broader oncolytic immunotherapy category as developers weigh endpoints, trial design, and combination strategies for the next interactions with regulators.