Ultragenyx completes rolling BLA submission to the FDA for DTX401, a potential first-in-class gene therapy targeting the root cause of Glycogen Storage Disease Type Ia.
Written By: Pharmacally Medical News Desk
Ultragenyx Pharmaceutical has completed the rolling submission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration for DTX401, an adeno-associated virus (AAV) gene therapy aimed at treating Glycogen Storage Disease Type Ia (GSDIa).
This submission is considered to be significant regulatory milestone as the company seeks the first approved therapy that directly targets the underlying cause of this rare, life-threatening metabolic disorder.
Rolling submission allows the FDA to review sections of the application as they are completed, potentially shortening review timelines
Ultragenyx says finishing the rolling BLA submission for DTX401 is an important milestone toward offering the first treatment that addresses the root cause of GSDIa. Even with strict diet and cornstarch therapy, patients continue to face acute hypoglycemia and long-term organ complications. The company plans to work closely with the FDA so the therapy can reach as many people with GSDIa as possible if approved.
What is GSDIa
Glycogen Storage Disease Type Ia (GSDIa) is a rare genetic disorder caused by mutations in the G6PC gene, leading to deficiency of the enzyme glucose-6-phosphatase. Without this enzyme, the liver cannot properly release glucose from glycogen or gluconeogenesis. Patients face severe hypoglycemia, enlarged liver, metabolic complications, and a heavy reliance on continuous dietary management, including frequent intake of uncooked cornstarch to maintain normal blood glucose. Conventional approaches do not correct the root defect, and there are no approved pharmacologic therapies for this condition.
DTX401: Mechanism and Delivery
DTX401 (Pariglasgene Brecaparvovec) is an investigational gene therapy delivered via a single intravenous infusion. It uses an AAV8 vector to introduce a functioning copy of the G6PC gene into liver cells, enabling stable expression of glucose-6-phosphatase. The goal is to restore more normal glucose regulation and reduce dependence on cornstarch and other external glucose sources.
Clinical Evidence Supporting the BLA
The BLA includes preclinical data and results from a development program that has treated 52 patients, with follow-up extending to six years. The cornerstone of the submission is the Phase 3 GlucoGene study (NCT05139316), a randomized, double-blind, placebo-controlled trial in patients aged 8 years and older with GSDIa.
In this study, DTX401 produced substantial reductions in daily cornstarch intake, averaging about a 41% decrease by Week 48 compared with roughly 10% in the placebo group. These reductions were achieved while maintaining low rates of hypoglycemia, increasing time spent in euglycemia, and improving fasting tolerance. Patients also reported meaningful improvements in quality of life. Overall, DTX401 was generally well tolerated, with most treatment-related events consisting of manageable elevations in liver transaminases.
Separate analyses continue to show durable reductions in cornstarch requirements over time, reinforcing the therapy’s potential to significantly reduce the day-to-day treatment burden for people living with GSDIa.
Regulatory Pathway and Designations
Ultragenyx has benefited from a rolling review process with the FDA, which allowed submission of parts of the BLA as they were completed. The recent milestone reflects submission of the final section on chemistry, manufacturing, and controls (CMC). DTX401 has earned multiple designations acknowledging its potential impact, including orphan drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy (RMAT) from the FDA. The European Medicines Agency has also granted orphan and PRIME designations.
References
Ultragenyx Completes Rolling Submission of Biologics License Application (BLA) to U.S. FDA for DTX401 AAV Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa), 30 December 2025, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-completes-rolling-submission-biologics-license
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
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 2025, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-positive-longer-term-data-phase-3-study