Ultragenyx Begins FDA Marketing Application for DTX401 Gene Therapy for GSD Type Ia

Ultragenyx Pharmaceutical has started the FDA marketing application process for its gene therapy, DTX401 AAV, to treat glycogen storage disease Type Ia. The company has already submitted some information to the FDA and will continue to provide more data in a rolling submission format.

Ultragenyx Pharmaceutical (NASDAQ: RARE) has taken a significant step forward in the development of its gene therapy, DTX401 AAV, for the treatment of Glycogen Storage Disease Type Ia (GSDIa). The company has initiated a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA), marking a substantial milestone in the regulatory process.

The rolling submission allows the FDA to begin reviewing the non-clinical and clinical modules of the BLA while Ultragenyx completes the chemistry, manufacturing, and controls (CMC) module, expected in the fourth quarter of 2025. The submission includes impressive 96-week Phase 3 data showing a 60% reduction in daily cornstarch requirements in the treatment group and a 64% reduction in the crossover placebo group. These reductions, even greater than at the 48-week timepoint, suggest durable and potentially increasing treatment effects.

The BLA submission addresses potential regulatory hurdles by incorporating lessons learned from the company's UX111 program, which previously received a complete response letter from the FDA. Specifically, Ultragenyx is working to resolve manufacturing facility observations that could otherwise delay approval, demonstrating regulatory sophistication and increasing the probability of first-cycle approval.

For GSDIa patients, who currently manage their condition through frequent large doses of cornstarch to prevent potentially life-threatening hypoglycemia, DTX401 represents a potentially transformative one-time treatment option. The significant reduction in cornstarch dependency shown in the clinical data would substantially reduce treatment burden and improve quality of life for these patients.

Ultragenyx's strategy of initiating a rolling BLA submission allows the FDA to begin reviewing the submitted non-clinical and clinical modules while the company proactively resolves any relevant CMC and facility questions. This approach increases the likelihood of a timely and successful regulatory review process.

The BLA for DTX401 includes the previously disclosed 96-week data from the randomized, placebo-controlled Phase 3 study, which demonstrated clinically significant reductions in total daily cornstarch requirements. It will also include updates to proactively respond to related FDA observations identified in the UX111 complete response letter in the CMC section and at the company’s gene therapy manufacturing facilities.

References:
[1] https://www.stocktitan.net/news/RARE/ultragenyx-initiates-rolling-submission-of-biologics-license-l8g61yk6xz0u.html