Ultragenyx Announces FDA Acceptance and Priority Review of Biologics License Application (BLA) for UX111, an AAV Gene Therapy for Sanfilippo Syndrome Type A (MPS IIIA)

NOVATO, Calif. — Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a leader in the development of novel therapies for rare and ultrarare genetic diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for UX111 (ABO-102), an investigational adeno-associated virus (AAV)-based gene therapy for the treatment of Sanfilippo syndrome type A (MPS IIIA), a rare, progressive, and fatal lysosomal storage disorder. The FDA has granted the BLA Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. Additionally, the FDA has informed Ultragenyx that it does not currently plan to hold an advisory committee meeting to discuss the application, streamlining the path toward potential approval.

A Potential First-in-Class Therapy for Sanfilippo Syndrome Type A

If approved, UX111 would become the first-ever treatment for Sanfilippo syndrome type A, offering hope to patients and families affected by this devastating disease. MPS IIIA is a neurodegenerative disorder characterized by the accumulation of heparan sulfate (HS) in cells, particularly in the brain, leading to rapid cognitive and motor decline, behavioral abnormalities, and early death. Currently, there are no approved therapies that address the underlying cause of the disease, making UX111 a potentially transformative advancement for the MPS IIIA community.

Clinical Data Supporting the BLA

The BLA submission is supported by robust clinical data from the pivotal Transpher A study and long-term follow-up, which were presented at the WORLDSymposium™ 2025. Key findings include:

• Reduction in Heparan Sulfate (HS):
  • Treatment with UX111 resulted in rapid and sustained reductions in heparan sulfate levels in cerebrospinal fluid (CSF), a key biomarker of disease progression. These reductions were observed regardless of the patient’s age or stage of disease at the time of treatment.
• Improvements in Cognitive and Communication Skills:
  • Patients treated with UX111 showed statistically significant improvements in cognition, receptive communication, and expressive communication, as measured by Bayley-III raw scores, compared to natural history data from untreated patients. These improvements were correlated with the reduction in CSF-HS levels, demonstrating the therapy’s potential to address both the biochemical and clinical manifestations of the disease.
• Safety Profile:
  • UX111 was generally well-tolerated, with the most common adverse events being elevations in liver enzymes, which were mild to moderate in severity (Grade 1 or 2) and resolved without intervention. No serious safety concerns, such as thrombotic microangiopathy (TMA) or atypical hemolytic uremic syndrome (aHUS), were observed.

About UX111: A Novel AAV-Based Gene Therapy

UX111 is a one-time, intravenous gene therapy designed to address the root cause of Sanfilippo syndrome type A by delivering a functional copy of the SGSH gene, which encodes the sulfamidase enzyme deficient in MPS IIIA patients.

• Mechanism of Action:
  • The therapy utilizes a self-complementary AAV9 vector, which has been engineered to efficiently deliver the SGSH gene to target cells. Once inside the cells, the gene enables the production of the sulfamidase enzyme, which is then secreted and taken up by neighboring cells. This process, known as cross-correction, helps reduce the accumulation of heparan sulfate and mitigates the progressive neurodegeneration associated with the disease.
• Regulatory Designations:
  • UX111 has received multiple regulatory designations, underscoring its potential to address an unmet medical need:
  • Regenerative Medicine Advanced Therapy (RMAT) and Fast Track Designation from the FDA.
  • Rare Pediatric Disease Designation and Orphan Drug Designation in the U.S.
  • PRIME (Priority Medicines) and Orphan Medicinal Product Designation in the European Union.

About Sanfilippo Syndrome Type A (MPS IIIA)

Sanfilippo syndrome type A is a rare, autosomal recessive lysosomal storage disease caused by mutations in the SGSH gene, which leads to a deficiency in the sulfamidase enzyme. This enzyme is responsible for breaking down heparan sulfate, a glycosaminoglycan that accumulates in cells throughout the body, particularly in the brain.

• Disease Progression:
  • Children with MPS IIIA typically appear normal at birth but begin to show symptoms between 2–6 years of age, including global developmental delay, cognitive decline, language and motor regression, hyperactivity, sleep disturbances, and aggressive behavior.
  • The disease progresses rapidly, leading to severe neurological impairment and early death, with a median life expectancy of 15 years.
• Prevalence:
  • MPS IIIA is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible regions worldwide.

Next Steps and Commercialization

• PDUFA Date: The FDA’s decision on the BLA is expected by August 18, 2025.
• Commercial Readiness: If approved, Ultragenyx plans to commercialize UX111 using its existing metabolic disease team, which has extensive experience in delivering therapies for rare genetic disorders. The company is committed to ensuring broad access to UX111 for eligible patients.

About Ultragenyx

Ultragenyx is a biopharmaceutical company dedicated to developing and commercializing novel therapies for serious rare and ultrarare genetic diseases. The company’s portfolio includes approved therapies and a robust pipeline of investigational treatments targeting diseases with high unmet medical needs and clear biological mechanisms.

• Mission and Strategy:
  • Ultragenyx’s mission is to improve the lives of patients with rare diseases by delivering safe, effective, and innovative therapies with urgency. The company’s strategy focuses on efficient drug development, leveraging cutting-edge science and technology to accelerate the delivery of treatments to patients.

The Broader Impact of UX111

The development of UX111 not only represents a potential breakthrough for Sanfilippo syndrome type A but also serves as a pioneering step in the treatment of other neuronopathic metabolic diseases. By demonstrating the feasibility of AAV-based gene therapy for lysosomal storage disorders, UX111 could pave the way for similar approaches to address other rare genetic diseases affecting the central nervous system.

Reference:
https://www.globenewswire.com/news-release/2025/02/18/3027767/20739/en/Ultragenyx-Announces-FDA-Acceptance-and-Priority-Review-of-the-Biologics-License-Application-BLA-for-UX111-AAV-Gene-Therapy-to-Treat-Sanfilippo-Syndrome-Type-A-MPS-IIIA.html

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