Ultragenyx Plans Accelerated Approval Filing for UX111 to Treat Sanfilippo Syndrome Type A

Ultragenyx Pharmaceutical Inc. has announced a successful agreement with the U.S. Food and Drug Administration (FDA) regarding the use of cerebral spinal fluid (CSF) heparan sulfate (HS) as a surrogate endpoint. This decision is pivotal for the accelerated approval process of UX111 (ABO-102) AAV gene therapy, aimed at treating Sanfilippo syndrome (MPS IIIA). The company plans to finalize the details of the Biologics License Application (BLA) with the FDA by late this year or early next year.

Emil D. Kakkis, M.D., Ph.D., CEO and President of Ultragenyx, expressed optimism, noting that this alignment with the FDA marks a significant milestone for the Sanfilippo syndrome community. He emphasized the urgent need for potentially life-saving therapies for children suffering from severe neurological diseases and acknowledged the contributions of patient and caregiver advocates, scientists, and industry leaders in providing the essential evidence for this decision.

The BLA submission will leverage data from ongoing clinical trials, including the pivotal Transpher A study, which assesses the safety and efficacy of UX111 in children with MPS IIIA. Recent results from both the Transpher A and long-term follow-up studies were presented at the 20th Annual WORLDSymposium™.

UX111 is an innovative in vivo gene therapy currently in Phase 1/2/3 development for treating Sanfilippo syndrome type A (MPS IIIA). This rare and fatal lysosomal storage disease primarily impacts the central nervous system (CNS) and currently has no approved treatments. The therapy involves a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. It aims to address the SGSH enzyme deficiency that leads to the abnormal accumulation of heparan sulfate in the brain, causing progressive cell damage and neurodegeneration.

The UX111 program has secured several important designations in the U.S., including Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations. In the European Union, it has received PRIME and Orphan medicinal product designations.

Sanfilippo syndrome type A (MPS IIIA) is characterized by rapid neurodegeneration, with symptoms appearing in early childhood. Children with MPS IIIA exhibit global developmental delays, which progressively worsen into language and cognitive decline, behavioral issues, and early death. The condition is estimated to affect around 3,000 to 5,000 patients in regions with accessible commercial medical services. The median life expectancy for those afflicted is approximately 15 years. The disease is caused by biallelic pathogenic variants in the SGSH gene, leading to a deficiency in the sulfamidase enzyme, essential for breaking down heparan sulfate. This enzymatic deficiency results in the accumulation of glycosaminoglycans in cells, driving the observed rapid neurodegeneration.

Ultragenyx is dedicated to developing innovative therapies for serious rare and ultra-rare genetic diseases. The company boasts a diverse range of approved therapies and product candidates designed to address conditions with significant unmet medical needs and well-defined biological targets. Ultragenyx's strategy centers on efficient drug development processes to deliver safe and effective treatments to patients urgently. The company is led by a management team with extensive experience in the development and commercialization of therapeutics for rare diseases.