Drugs

Denali Aims for Early 2025 Hunter Syndrome BLA

Denali Therapeutics says it is on track to submit a BLA early next year that will seek accelerated approval for DNL310 (tividenofusp alfa) and its use in treating Mucopolysaccharidosis Type II (MPS II, aka Hunter syndrome). The company says its projection is based on feedback from the agency during a meeting with CDER reviewers that resulted in an agreement that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support the therapy’s accelerated approval in MPS II.

“Based on discussions with CDER, Denali will include preclinical and clinical data on biomarkers (CSF HS and neurofilament light (NfL)) and safety in the BLA…,” the company says. “We also look forward to plans for conversion to full approval following completion of the global Phase 2/3 COMPASS study.”

Denali says data from a Phase 1/2 study show that treatment with tividenofusp alfa produces robust and durable effects, including “normalization of key disease biomarkers and improvement or stabilization in associated [central nervous system] CNS and somatic clinical endpoints.” It says data from the study also showed:

A 90% mean reduction in CSF HS from baseline at Week 24, with a sustained reduction through Week 104
Proportion of participants with normal total urine glycosaminoglycans increased from 5% of participants at baseline to 77% at Week 24
Sustained reduction of serum NfL from baseline with all participants who had reached Week 129 having normal or near normal levels
Tividenofusp alfa was generally well tolerated, with a safety profile that continues to support its development

Hunter syndrome is described as a rare genetic disease that affects over 2,000 individuals worldwide, leading to behavioral, cognitive, and physical symptoms ultimately resulting in a shortened lifespan. It is caused by mutations in the iduronate-2-sulfatase (IDS) gene, which leads to a deficiency of the IDS enzyme responsible for the breakdown of the glycosaminoglycans heparan and dermatan sulfate in lysosomes.

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