Ultragenyx initiates rolling BLA for AAV gene therapy for glycogen storage disease

Ultragenyx Pharmaceutical has initiated the rolling submission of its BLA seeking approval for DTX401, an AAV gene therapy as a treatment for glycogen storage disease type Ia, a serious inherited disease that results in the inability to regulate blood sugar.

Ultragenyx has submitted the nonclinical and clinical modules to the FDA and plans to complete the full BLA including submission of the chemistry, manufacturing and controls (CMC) module in the fourth quarter of 2025.

DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon and cortisol. It’s administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression.

The BLA will also include updates to proactively respond to related FDA observations identified in the complete response letter issued in July for Ultragenyx’s BLA for UX111, an AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). The CRL cited specific CMC-related observations from recently completed manufacturing facility inspections that Ultragenyx says are resolvable as they are “related to facilities and processes and are not directly related to the quality of the product.”

“By granting a rolling review, the FDA can begin reviewing the nonclinical and clinical sections of the BLA, where we demonstrate the clinically significant reduction in cornstarch burden and improved clinical outcomes, while we proactively resolve any relevant CMC and facility questions that were learned in our UX111 program. Over the next few months, we expect to resolve the FDA’s observations and then complete our DTX401 BLA submission in the fourth quarter of this year,” said Eric Crombez, MD, chief medical officer at Ultragenyx.