The FDA granted Replimune accelerated approval for its engineered oncolytic-virus therapy Tudriqev (formerly RP1) in advanced melanoma, ending a two-time rejection saga. The treatment was cleared for use with Bristol Myers Squibb’s Opdivo in patients whose disease progressed after PD-1 immunotherapy, based on a single-arm dataset showing tumor responses in about one quarter of enrollees with a median duration just over 14 months. Regulators relied on a panel-supported efficacy signal despite FDA reviewers raising concerns about trial design and response assessment. Replimune’s confirmatory Phase 3 trial testing Tudriqev-Opdivo versus PD-1 therapy or chemotherapy is expected in late 2027, keeping the approval contingent on confirmatory results. Separately, the FDA approved Takeda’s Orzeyful (oveporexton), the first orexin receptor 2 agonist designed to address the underlying biology of narcolepsy type 1 in adults. The clearance follows pivotal efficacy and safety data versus placebo in adults, and it may prompt a reassessment of treatment approaches in sleep-disorder care. Taken together, the two approvals underscore a continuing regulatory shift toward both earlier mechanistic targeting in neurologic disease and accelerated pathways for immuno-oncology combinations in hard-to-treat populations.