Ultragenyx Begins FDA Submission for GSDIa AAV Gene Therapy

NOVATO, Calif.—Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) announced on Monday, August 18, 2025, that it has started a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its Adeno-associated virus (AAV) gene therapy, DTX401, for the treatment of Glycogen Storage Disease Type Ia (GSDIa).

A New Hope for GSDIa Patients

Currently, patients with GSDIa must consume large, frequent doses of cornstarch to avoid life-threatening drops in blood sugar. DTX401 is an AAV gene therapy, a type of treatment that uses a modified, non-disease-causing virus called an AAV as a delivery vehicle, or “vector.” This vector is engineered to carry a healthy copy of a gene into a patient’s cells to correct a genetic defect.

In the case of DTX401, the AAV vector is designed to deliver a working copy of the G6Pase-α gene to liver cells, enabling the body to produce the missing enzyme and regulate blood sugar naturally. This single-infusion treatment could significantly reduce or eliminate the daily burden on patients.

“Initiating the BLA for DTX401…is an important milestone for this much-needed treatment option,” said Dr. Eric Crombez, Ultragenyx’s chief medical officer. He noted that the rolling review process will allow the FDA to begin reviewing the non-clinical and clinical data while the company resolves manufacturing-related questions.

The company has already submitted the non-clinical and clinical portions of the BLA and expects to complete the full submission by the fourth quarter of 2025.

Promising Clinical Results

The BLA submission is supported by 96-week data from a Phase 3 study. The study showed that patients receiving DTX401 experienced a significant reduction in their total daily cornstarch intake. The data showed a 60% reduction in cornstarch for one group and a 64% reduction for another group, demonstrating a sustained and meaningful improvement in managing the disease.

The FDA has already granted DTX401 several key designations, including:

• Orphan Drug Designation
• Regenerative Medicine Advanced Therapy (RMAT)
• Fast Track Designation

These designations are given to therapies that address serious conditions with an unmet medical need and are intended to expedite the review process.

What is Glycogen Storage Disease Type Ia?

GSDIa is a rare genetic disorder where a defective gene prevents the body from properly regulating blood sugar. This can lead to dangerously low blood sugar levels (hypoglycemia) and the buildup of glycogen in the liver and other organs, which can cause severe health complications and, if left untreated, can be fatal in infancy or childhood. With no approved medications currently available, GSDIa affects an estimated 6,000 people globally.