FDA cleared Denali Therapeutics’ Avlayah (tividenofusp alfa) for Hunter syndrome under the accelerated approval pathway, a notable decision as the agency has recently rejected several rare disease submissions amid political and evidentiary pressure. Denali’s approval reverses uncertainty that followed earlier rare disease failures in the category. Avlayah targets a rare lysosomal storage disorder for patients with MPS II, using a gene-directed approach designed to restore functional activity. The approval came on the heels of an FDA stance requiring more clinical data for other rare disease programs, which had raised concerns among advocates about the agency’s appetite for expedited review. For Denali, the clearance provides a new path for label access and lifecycle development. For the broader field, the decision signals that accelerated programs can still advance when the totality of evidence meets FDA’s threshold. The approval also reinforces the importance of designing rare disease trials to satisfy regulators’ expectations for both clinical relevance and dataset completeness.