The US Food and Drug Administration has granted accelerated approval to tividenofusp alfa, marking a significant advance in the treatment of neurologic manifestations of Hunter syndrome, a rare lysosomal storage disorder.
The therapy, marketed as Avlayah, is the first enzyme replacement treatment specifically engineered to cross the blood brain barrier, enabling direct targeting of central nervous system involvement. Hunter syndrome, also known as mucopolysaccharidosis type II, is caused by a deficiency of the enzyme iduronate 2 sulfatase, leading to accumulation of glycosaminoglycans in tissues, including the brain. Existing treatments have not been able to address neurological symptoms due to their inability to penetrate the brain.
Tividenofusp alfa uses a novel fusion protein approach, combining the missing enzyme with a transport mechanism that facilitates delivery across the blood brain barrier. This allows the therapy to reach both peripheral tissues and the central nervous system, addressing a longstanding unmet clinical need.
The approval was based on data from an ongoing phase 1/2 study involving paediatric patients. Results showed substantial reductions in biomarkers associated with disease activity, including around 91% reductions in cerebrospinal fluid heparan sulfate levels at 24 weeks, with most patients achieving normalisation. Improvements were also observed in markers of neuroaxonal injury and in early measures of cognitive and adaptive function.
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The therapy demonstrated a generally consistent safety profile, with most adverse events reported as mild to moderate. Infusion related reactions were among the most common side effects.
Accelerated approval was granted based on biomarker evidence considered reasonably likely to predict clinical benefit. Continued approval will depend on confirmation from the ongoing phase 2/3 COMPASS trial, which is evaluating longer term outcomes across a broader patient population.
Experts say the development represents a major milestone, as it introduces a new strategy for delivering biologic therapies to the brain and may have implications for other neurological and rare genetic disorders.
This news item has been summarised using AI and checked by humans before publication.
Sources
Denali Therapeutics press release
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