Ultragenyx Pharmaceuticals Announces FDA Acceptance of Gene Therapy BLA for Sanfilippo Syndrome Type A
February 18, 2025 – Novato, California – Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has announced that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for UX111 (ABO-102), an adeno-associated virus (AAV) gene therapy intended to treat Sanfilippo syndrome type A (MPS IIIA). The FDA has granted the application Priority Review status with a Prescription Drug User Fee Act (PDUFA) target action date set for August 18, 2025. Notably, the FDA has indicated it does not currently plan to convene an advisory committee meeting to evaluate this application.
Advancing a Novel Treatment for Sanfilippo Syndrome Type A
Emil D. Kakkis, M.D., Ph.D., CEO and President of Ultragenyx, expressed optimism about the development, noting that acceptance of the UX111 BLA brings the company closer to delivering the first-ever treatment for Sanfilippo syndrome type A. He highlighted the potential of the UX111 program to pave the way for accelerated approval of therapies addressing neuronopathic mucopolysaccharidoses (MPS) and other metabolic brain diseases.
Clinical Evidence Supporting UX111’s Approval
The BLA submission is supported by comprehensive clinical data, including recent results presented at WORLDSymposium™ 2025 from the ongoing pivotal Transpher A trial and long-term follow-up studies. These findings demonstrate that a single intravenous administration of UX111 leads to a rapid and sustained reduction in cerebrospinal fluid (CSF) levels of heparan sulfate (HS) — a hallmark of Sanfilippo syndrome type A — regardless of patient age or disease stage at treatment initiation.
Furthermore, the data revealed statistically significant improvements in cognitive domains, expressive, and receptive communication among treated patients compared to untreated natural history controls. These cognitive benefits were tightly correlated with decreased CSF-HS levels. The most common treatment-related adverse effects observed were mild to moderate increases in liver enzyme levels, all of which resolved without lasting complications.
What Is UX111?
UX111 is an innovative one-time gene therapy designed to address the root cause of Sanfilippo syndrome type A—a fatal lysosomal storage disorder characterized by deficient activity of the sulfamidase (SGSH) enzyme. This deficiency results in the accumulation of heparan sulfate in the brain, causing progressive neurodegeneration and severe neurological decline.
Utilizing a self-complementary AAV9 vector, UX111 delivers a functional copy of the SGSH gene to patient cells via intravenous infusion. The treated cells then produce and secrete the functional enzyme, which can be taken up by neighboring brain cells, effectively cross-correcting the enzyme deficiency.
Originally developed by Abeona Therapeutics, the program was subsequently transferred to Ultragenyx for completion. The therapy has received several regulatory designations in the U.S., including Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Rare Pediatric Disease, and Orphan Drug status, as well as PRIME and Orphan medicinal product status in the European Union. If approved, Ultragenyx will launch UX111 through its established metabolic disease clinical and commercial infrastructure.
Understanding Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo syndrome type A is a rare, inherited lysosomal storage disorder primarily affecting the central nervous system. It manifests in early childhood with delayed developmental milestones, followed by a relentless decline in cognitive, language, and motor functions, along with behavioral issues, ultimately leading to premature death. The median life expectancy for affected patients is approximately 15 years.
This devastating disease stems from pathogenic mutations in both copies of the SGSH gene, resulting in deficient sulfamidase enzyme activity. Without this enzyme, heparan sulfate, a glycosaminoglycan, accumulates excessively within cells, triggering widespread neurodegeneration.
The disorder is estimated to affect between 3,000 and 5,000 individuals in regions with commercial access to advanced therapies.
About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company dedicated to developing and commercializing novel treatments for serious rare and ultra-rare genetic diseases. Focused on diseases with limited or no approved therapies, the company aims to efficiently advance drug development based on well-understood biology to meet urgent unmet medical needs.
Led by a seasoned management team with experience in rare disease therapeutics, Ultragenyx prioritizes rapid, cost-effective development and delivery of safe, effective treatments to patients worldwide.
Forward-Looking Statements
The announcement contains forward-looking statements related to the progress and expectations for UX111’s clinical development, regulatory review, and commercialization potential. These statements are subject to risks and uncertainties, including the unpredictable nature of clinical trials, regulatory approval challenges, possible adverse effects, reliance on collaborators, competition, market size, manufacturing risks, and financial factors.
Ultragenyx disclaims any obligation to update these forward-looking statements post-publication. For detailed risk factors, the company refers to its filings with the U.S. Securities and Exchange Commission (SEC).
Media and Investor Contacts
- Investors: Joshua Higa – +1-415-475-6370, [email protected]
- Media: Carolyn Wang – +1-415-225-5050, [email protected]