Tividenofusp Alfa Gets Priority Review for Hunter Syndrome

The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for tividenofusp alfa for the treatment of Hunter syndrome, also known as mucopolysaccharidoses type II (MPS II).  

MPS II is a rare genetic lysosomal storage disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. This leads to a deficiency of the IDS enzyme resulting in glycosaminoglycan accumulation and organ dysfunction.

Tividenofusp alfa is a novel central nervous system-penetrant enzyme replacement therapy designed to address the neurological manifestations of MPS II by delivering IDS into the brain and body. The BLA acceptance was supported by data from an open-label, single-arm, phase 1/2 study (ClinicalTrials.gov Identifier: NCT04251026), which evaluated the safety, pharmacokinetics, and pharmacodynamics of tividenofusp alfa in 47 pediatric participants up to 18 years of age with MPS II. 

An interim analysis of findings showed patients treated with tividenofusp alfa experienced significant reductions in central nervous system and peripheral biomarkers of disease. This included a 90% mean reduction in cerebrospinal fluid heparan sulfate from baseline at week 24, with all patients having normal or near normal levels at week 24 (reductions were sustained through week 104). Additionally, the proportion of patients with normal total urine GAGs increased from 5% at baseline to 77% at week 24; this effect was sustained through week 129.

Results also showed a significant reduction in serum neurofilament light, a marker of neurodegeneration. Improvements in adaptive behavior, cognitive scores, hearing, liver volume, and growth outcomes were also noted. 

The most common treatment-related adverse events were infusion-related reactions, anemia, vomiting, pyrexia, respiratory infections, and rash.

“If FDA-approved, tividenofusp alfa would mark the first significant advancement in nearly two decades for enzyme replacement therapy for individuals living with Hunter syndrome because of its potential for delivery to tissues throughout the brain and the body,” said Carole Ho, MD, Chief Medical Officer and Head of Development of Denali Therapeutics.

Denali Therapeutics has filed for accelerated approval of tividenofusp alfa in MPS II. A Prescription Drug User Fee Act target date of January 5, 2026 has been assigned to the application.

The Company is currently conducting the phase 2/3 COMPASS trial (ClinicalTrials.gov Identifier: NCT05371613) evaluating tividenofusp alfa in pediatric and young adult participants with neuronopathic or non-neuronopathic MPS II. The study is expected to serve as the confirmatory trial for conversion to full approval. 

This article originally appeared on MPR