Ultragenyx Completes FDA BLA Submission for DTX401, Paving the Way for the First AAV Gene Therapy to Treat GSDIa

NOVATO, CA —December 30, 2025— Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) announced today the completion of its rolling Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for DTX401 (pariglasgene brecaparvovec). If approved, the AAV-based treatment would become the first therapy to address the underlying genetic cause of Glycogen Storage Disease Type Ia (GSDIa), a life-threatening metabolic disorder.

GSDIa is caused by mutations in the G6PC gene, which leads to a deficiency in the G6Pase enzyme. This enzyme is essential for the liver to release glucose into the bloodstream. Without it, patients suffer from severe, life-threatening hypoglycemia and must adhere to a grueling regimen of around-the-clock cornstarch intake to maintain blood sugar levels.

DTX401 utilizes an AAV8 viral vector to deliver a functional copy of the G6PC gene directly to liver cells. Unlike traditional management, this AAV gene therapy is designed to:

• Restore Enzyme Activity: Enable liver cells to produce active G6Pase.

• Hormonal Regulation: Allow the liver to respond naturally to insulin and cortisol signals.

• Reduce Glycogen Buildup: Lower hepatic glycogen levels, a key biomarker of the disease.Robust Clinical Evidence

Robust Clinical Evidence

The BLA submission is supported by a comprehensive clinical program involving 52 patients with up to six years of follow-up. Data from the Phase 3 GlucoGene study highlighted several transformative benefits:

• Cornstarch Reduction: Significant decrease in the quantity and frequency of daily cornstarch requirements.

• Improved Glucose Stability: Enhanced fasting tolerance and maintenance of euglycemia (normal blood sugar).

• Quality of Life: Meaningful improvements reported by patients on the Global Impression of Change (PGIC) scale.

Regulatory Milestones and Next Steps

The FDA has previously granted DTX401 several high-priority designations, including Fast Track, RMAT, and Orphan Drug status. With the submission of the final Chemistry, Manufacturing, and Controls (CMC) module, the FDA will now review the package to determine if the therapy meets the criteria for commercial approval.

“The completion of our BLA submission is a significant step toward delivering the first therapy that directly targets the underlying cause of GSDIa,” said Dr. Eric Crombez, Chief Medical Officer at Ultragenyx. “We look forward to providing this potentially life-changing therapy to the estimated 6,000 people living with this condition.”