Denali approval revives surrogate-endpoint path in neuronal MPS

The first U.S. approval of a brain shuttle-enabled protein therapy gives Denali its first product and suggests continued FDA openness to biomarker-based approvals in severe rare disease.

FDA granted accelerated approval Wednesday to Denali Therapeutics Inc. (NASDAQ:DNLI) for Avlayah tividenofusp alfa-eknm, an enzyme replacement therapy designed to cross the blood-brain barrier to treat the neurologic manifestations of mucopolysaccharidosis type II (MPS II), or Hunter syndrome. The decision was based on reduction of heparan sulfate in the cerebrospinal fluid, a biomarker of restored enzyme activity...