Ultragenyx Scores FDA Priority Review for DTX401 in Rare Metabolic Disorder

Ultragenyx Pharmaceutical Inc. has reached a key milestone in treating Glycogen Storage Disease Type Ia (GSDIa), a rare and debilitating metabolic disorder. The U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) for DTX401 (pariglasgene breparvovec), an investigational AAV gene therapy. Granted Priority Review status, the FDA set a Prescription Drug User Fee Act (PDUFA) target action date of August 23, 2026, signaling a potential fast-track path to approval.

A Breakthrough for GSDIa Patients

GSDIa stems from mutations in the G6PC gene, which impairs the enzyme glucose-6-phosphatase (G6Pase). This enzyme is essential for releasing glucose from glycogen stores and other sources during fasting, preventing severe hypoglycemia dangerously low blood sugar levels that can lead to life-threatening episodes, especially at night.

Patients also face long-term complications like enlarged liver, kidney issues, and metabolic imbalances due to glycogen buildup.

Current management relies on frequent cornstarch doses every few hours, including overnight feeds, to mimic glucose release.

As noted by Ultragenyx’s Chief Medical Officer Eric Crombez, M.D., “this place an extraordinary burden on individuals and families while still leaving significant medical needs unmet.” No approved drugs exist, affecting an estimated 6,000 people in accessible markets.

 How DTX401 Works

DTX401 uses adeno-associated virus (AAV8) to deliver a functional copy of the G6PC gene directly to liver cells. Under the native promoter’s control, it enables stable G6Pase expression, allowing treated cells to respond to natural hormonal signals like insulin and cortisol for glucose regulation.

Administered as a one-time intravenous infusion, preclinical data showed restored enzyme activity, reduced hepatic glycogen, and slowed disease progression.

Clinical Basis

The BLA draws from a robust program involving 52 patients and up to six years of follow-up. Pivotal Phase 3 GlucoGene trial (NCT05139316) results randomized, double-blind, and placebo-controlled highlighted DTX401’s efficacy:

• Significant cuts in daily cornstarch intake (quantity and frequency).
• Maintained low hypoglycemia rates.
• Better euglycemia (normal blood sugar) and fasting tolerance.
• Quality-of-life gains per Patient Global Impression of Change (PGIC) scores.

Safety was favorable, with good tolerability.

If approved, DTX401 would launch from Ultragenyx’s new U.S.-based gene therapy facility in Bedford, Massachusetts, ensuring domestic manufacturing.

Regulatory Momentum

DTX401 holds multiple FDA designations: Rare Pediatric Disease, Orphan Drug, Fast Track, and Regenerative Medicine Advanced Therapy (RMAT). The European Medicines Agency (EMA) has granted Orphan Drug and PRIME status, paving the way for potential global access.

This filing underscores gene therapy’s promise for inborn errors of metabolism, offering a one-time fix over lifelong dietary regimens. Ultragenyx continues collaborating with the FDA through review.

Reference

Ultragenyx Announces U.S. FDA Acceptance and Priority Review of the Biologics License Application (BLA) for DTX401 AAV Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa), 23 February 2026, Ultragenyx Announces U.S. FDA Acceptance and Priority Review of the Biologics License Application (BLA) for DTX401 AAV Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa)—Ultragenyx Pharmaceutical Inc.

Ultragenyx Announces Positive Longer-term Data from Phase 3 Study of DTX401 AAV Gene Therapy for the Treatment of Glycogen Storage Disease Type Ia (GSDIa), 08 September 2026, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-positive-longer-term-data-phase-3-study

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients with Glycogen Storage Disease Type Ia (GSDIa), ClinicalTrials.gov ID NCT05139316, https://clinicaltrials.gov/study/NCT05139316