US-based biotech Ultragenyx Pharmaceutical Inc., (NASDAQ: RARE) announced that the US FDA has accepted a Biologics License Application (BLA) for DTX401 (pariglasgene brecaparvovec), an AAV8-mediated gene therapy designed to deliver a functional copy of the G6PC gene for the treatment of glycogen storage disease type Ia (GSDIa). The agency granted the filing Priority Review status and assigned a Prescription Drug User Fee Act (PDUFA) action date of August 23, 2026.
Ultragenyx developed DTX401 internally following its 2017 acquisition of Dimension Therapeutics, the program’s originator, and plans to manufacture the product at its own gene therapy facility in Bedford, Massachusetts.
The FDA priority review designation for DTX401 reflects the current lack of any approved pharmacologic options for GSDIa. The BLA is supported by data from 52 treated patients with up to six years of follow-up, including results from the randomized, double-blind, placebo-controlled Phase III GlucoGene study. DTX401 has also received Rare Pediatric Disease designation, orphan drug designation, Fast Track designation, and regenerative medicine advanced therapy (RMAT) designation from the US FDA, as well as orphan drug and PRIority MEdicines (PRIME) designations from the European Medicines Agency.
DTX401 gene therapy mechanism and clinical program
DTX401 (pariglasgene brecaparvovec) is an investigational AAV8 gene therapy that delivers a functional copy of the glucose-6-phosphatase (G6PC) gene to hepatocytes via a single intravenous infusion. The G6PC gene encodes the enzyme glucose-6-phosphatase-alpha (G6Pase-α), which is essential for the final step of glycogenolysis and gluconeogenesis in the liver, enabling the release of free glucose into the bloodstream. In patients with GSDIa, pathogenic variants in G6PC result in absent or deficient G6Pase-α activity, leading to severe fasting hypoglycemia, excessive hepatic glycogen accumulation, metabolic derangements including lactic acidosis and hyperlipidemia, and long-term complications such as hepatic adenomas and renal disease. The current standard of care consists of frequent oral uncooked cornstarch or continuous glucose feeds to prevent hypoglycemic episodes, a regimen that imposes a lifelong burden on patients and families without addressing the underlying enzymatic deficiency.
DTX401 is designed to restore G6Pase-α activity in transduced liver cells under control of the native G6PC promoter, allowing treated hepatocytes to respond to normal hormonal signals including insulin and cortisol. Preclinical studies demonstrated improved G6Pase activity and reduced hepatic glycogen levels following administration. The clinical development program for GSDIa gene therapy with DTX401 includes three registered studies: a Phase I/II open-label, dose-escalation safety and dose-finding study in adults with GSDIa; a Phase III pivotal study (GlucoGene) evaluating percent change in daily cornstarch intake at Week 48 as the primary endpoint; and a long-term monitoring program tracking durability and safety in previously treated patients.