The FDA approved Denali Therapeutics’ Avlayah (tividenofusp alfa) for Hunter syndrome, marking a notable rare-disease decision after heightened scrutiny of the category. The approval came via accelerated approval, giving patients a new option that leverages Denali’s brain-shuttle-enabled delivery approach to cross the blood–brain barrier. Denali’s approval arrives after recent rejections in Hunter syndrome drug development, including an FDA refusal of a gene therapy from Regenxbio over clinical-data expectations. Avlayah was therefore under a close market spotlight as the FDA’s rare disease posture tightened. Separate FDA coverage also framed the approval as a way the agency may revive reliance on surrogate-endpoint pathways in neuronal mucopolysaccharidoses, highlighting how endpoints and delivery platforms are being evaluated in the post-accelerated-approval landscape.