Denali Therapeutics announces approval of AVLAYAH for the treatment of hunter syndrome

Denali Therapeutics announced the U.S. FDA has recently granted accelerated approval for AVLAYAH, which is the first FDA-approved biologic specifically designed to cross the blood-brain barrier and reach the whole body, including the brain. AVLAYAH is an enzyme replacement therapy indicated for the treatment of neurologic manifestations of Hunter syndrome when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment.

“The approval of AVLAYAH is a new era for the Hunter syndrome community as we deliver the first FDA-approved therapy designed to cross the brain’s protective barrier for individuals and families living with this debilitating disease. This approval reflects the determination and partnership of the MPS community, as well as the FDA’s collaborative engagement to incorporate biomarker evidence to help accelerate the development of urgently needed treatments,” said Ryan Watts, Ph.D., co-founder and Chief Executive Officer of Denali Therapeutics. “This milestone validates our TransportVehicle platform and its potential to overcome the long-standing challenge of delivering biologic medicines across the blood-brain barrier, with the aim to transform the treatment of a wide range of neurodegenerative diseases, lysosomal storage disorders and other serious diseases that impact millions worldwide.”

Hunter syndrome is a rare genetic disease caused by a deficiency in the iduronate 2-sulfatase enzyme, which is needed to break down complex sugars called glycosaminoglycans. In individuals with Hunter syndrome, GAGs build up in cells throughout the body, including the brain, resulting in progressive damage to organs and tissues beginning at a young age.

“The FDA approval of AVLAYAH represents a breakthrough advance as the first therapeutic innovation for the Hunter syndrome community in nearly 20 years,” said Joseph Muenzer, M.D., Ph.D., lead investigator of the AVLAYAH Phase 1/2 clinical trial, Director of the Muenzer MPS Research and Treatment Center and the Bryson Distinguished Professor in Pediatric Genetics at the University of North Carolina at Chapel Hill. “The neurologic manifestations of Hunter syndrome, which affect nearly all patients, have been one of the most challenging and persistent medical needs for the community and a central focus of many years of scientific research. As the first FDA-approved, brain-penetrant medicine for Hunter syndrome, AVLAYAH will substantially change how we treat patients and has the potential to become a new standard of care.”

Note that the approval of AVLAYAH is based on the reduction of a key disease biomarker, cerebrospinal fluid heparan sulfate, as a surrogate endpoint reasonably likely to predict clinical benefit in the treatment of neurologic manifestations of Hunter syndrome.

“Today’s accelerated approval of AVLAYAH is an important advancement for the Hunter syndrome community as the first and only enzyme replacement therapy designed to reach the central nervous system and periphery that is now FDA-approved to treat neurologic manifestations for individuals living with this disease. We extend our sincere gratitude to the study participants and families, investigators, clinicians and advocates whose courage and commitment made the approval of AVLAYAH possible,” said Peter Chin, M.D., Chief Medical Officer and Head of Development of Denali Therapeutics. “We continue to study AVLAYAH in our Phase 2/3 COMPASS study with the goal of confirming the clinical evidence across the MPS II patient spectrum.”

“This accelerated approval for MPS II based on a biomarker as a surrogate endpoint is an extraordinary day for the MPS and rare disease community. It represents both recognition that time matters profoundly for families affected by these devastating disorders and the potential to accelerate drug development more broadly across MPS and other rare diseases,” said Terri Klein, President and Chief Executive Officer of the National MPS Society. “This approval affirms that when strong science and advocacy come together, meaningful change, continued progress and hope are possible for individuals living with MPS and other rare diseases who are waiting for treatments.”

“For families living with Hunter syndrome, progress has often felt incremental while the disease itself continues to move relentlessly forward. For many, disease progression includes cognitive impacts that can add emotional weight to an already challenging diagnosis,” said Kristin McKay, President and Executive Director of Project Alive and parent of a child with Hunter syndrome. “Families have been waiting for new options that reach the brain, so the availability of this new therapeutic approach brings renewed optimism and hope for our community.”

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Related Topics and Keywords

AVLAYAH, denali therapeutics, hunter syndrome