Ultragenyx Initiates BLA Submission for DTX401 Gene Therapy in GSDIa.

Ultragenyx Pharmaceutical has initiated a rolling submission of a Biologics License Application to the FDA for DTX401 AAV gene therapy to treat Glycogen Storage Disease Type Ia. The company has submitted non-clinical and clinical modules, with the full BLA to be completed by Q4 2025. The treatment aims to address the current need for frequent cornstarch doses to prevent potentially life-threatening hypoglycemia.

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has initiated a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for DTX401, an investigational AAV gene therapy aimed at treating Glycogen Storage Disease Type Ia (GSDIa). The company has submitted the non-clinical and clinical modules of the BLA and plans to complete the full submission, including the chemistry, manufacturing, and controls (CMC) module, by the fourth quarter of 2025 [1].

DTX401 is designed to deliver stable expression and activity of G6Pase-α under control of the native promoter, allowing treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon, and cortisol. The gene therapy is administered as a single intravenous infusion and has demonstrated improvements in G6Pase-α activity and reductions in hepatic glycogen levels, a biomarker of disease progression [1].

The rolling submission strategy allows the FDA to begin reviewing the non-clinical and clinical sections of the BLA while Ultragenyx completes the CMC module. The BLA includes 96-week Phase 3 study data showing significant reductions in total daily cornstarch requirements. In the ongoing DTX401 group, patients experienced a 60% reduction, while those in the Crossover Placebo to DTX401 group saw a 64% reduction compared to baseline. These reductions are greater than those observed at the 48-week timepoint, suggesting durable and potentially increasing treatment effects [1].

The BLA submission will also address FDA observations from the UX111 complete response letter regarding CMC and manufacturing facilities. By proactively resolving these observations, Ultragenyx aims to increase the probability of first-cycle approval for DTX401 [2].

GSDIa is a serious inherited glycogen storage disease caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Patients with GSDIa are at risk of life-threatening hypoglycemia and may experience severe lactic acidosis, renal failure, and potentially die in infancy or childhood if left untreated. Currently, there are no approved pharmacologic therapies for GSDIa, which affects approximately 6,000 people in commercially accessible geographies [1].

Ultragenyx Pharmaceutical is a biopharmaceutical company committed to bringing novel therapies to patients with serious rare and ultra-rare genetic diseases. The company's strategy focuses on time- and cost-efficient drug development to deliver safe and effective therapies to patients with high unmet medical needs [1].

References:
[1] https://finance.yahoo.com/news/ultragenyx-initiates-rolling-submission-biologics-120000140.html
[2] https://www.stocktitan.net/news/RARE/ultragenyx-initiates-rolling-submission-of-biologics-license-l8g61yk6xz0u.html