Ultragenyx Files BLA to FDA for UX111 Gene Therapy for Sanfilippo Syndrome Type A

On December 19, 2024, Ultragenyx Pharmaceutical Inc. announced that it has filed a Biologics License Application with the U.S. Food and Drug Administration for UX111 (ABO-102), an AAV gene therapy intended for patients with Sanfilippo syndrome type A (MPS IIIA). This application seeks accelerated approval, marking a significant milestone for a community that has faced numerous challenges in finding effective treatments.

Emil D. Kakkis, the CEO and president of Ultragenyx, highlighted the difficulties encountered by the Sanfilippo community as they have watched the degeneration of their children's abilities, such as speaking and walking, leading to early death. He praised the FDA's acceptance of cerebral spinal fluid (CSF) heparan sulfate (HS) as a biomarker to support the accelerated approval path for mucopolysaccharidoses (MPS) disorders, including Sanfilippo syndrome. This acceptance has enabled Ultragenyx to file their BLA, which could pave the way for future therapies targeting these devastating diseases affecting the brain.

Earlier in the year, Ultragenyx and the FDA reached an agreement to use CSF HS as a surrogate endpoint for accelerated approval. This decision was based on extensive data presented by the company and a consortium of academics and industry sponsors at a workshop facilitated by the Reagan-Udall Foundation for the FDA in February 2024.

The supporting data for the BLA submission for UX111 come from ongoing studies, particularly the pivotal Transpher A study. Findings show that UX111 treatment leads to rapid and sustained reductions in HS levels in the CSF of patients with Sanfilippo syndrome type A. This sustained reduction correlates with better long-term cognitive development, contrasting with the decline observed in natural history data. The most commonly reported side effects were elevations in liver enzymes, with most adverse events being mild to moderate in severity and resolving over time.

UX111 is a cutting-edge in vivo gene therapy under Phase 1/2/3 development for treating Sanfilippo syndrome type A, a rare lysosomal storage disease primarily affecting the brain for which there is no approved treatment. The therapy involves a one-time intravenous infusion using a self-complementary AAV9 vector to introduce a functional SGSH gene into cells. This approach targets the SGSH enzyme deficiency that causes abnormal heparan sulfate accumulation in the brain, leading to cell damage and neurodegeneration. The UX111 program has received several designations, including Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug in the U.S., as well as PRIME and Orphan medicinal product designations in the EU.

Sanfilippo syndrome type A (MPS IIIA) is a severe lysosomal storage disorder with a rapid neurodegenerative progression starting in early childhood. Affected children experience developmental delays, which progress to language and cognitive decline, behavioral issues, and early death. It is estimated to affect 3,000 to 5,000 patients in accessible markets, with a median life expectancy of 15 years. The condition results from biallelic pathogenic variants in the SGSH gene, leading to a deficiency in the enzyme sulfamidase. This deficiency prevents proper breakdown of heparan sulfate, causing its accumulation and the associated neurodegenerative symptoms.

Ultragenyx is a biopharmaceutical company dedicated to developing innovative treatments for serious rare and ultra-rare genetic diseases. The company has a diverse portfolio of approved therapies and candidates designed to address diseases with significant unmet medical needs. Led by a team experienced in rare disease therapeutics development and commercialization, Ultragenyx aims for efficient drug development to swiftly deliver safe and effective therapies to patients.