Ultragenyx Initiates Rolling Submission of Biologics License Application (BLA) to U.S. FDA for DTX401 AAV Gene Therapy for the Treatment of Glycogen Storage Disease Type Ia (GSDIa)

NOVATO, Calif., Aug. 18, 2025 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced the initiation of a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval for DTX401 AAV gene therapy as a treatment for Glycogen Storage Disease Type Ia (GSDIa). The company has submitted the non-clinical 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.

“Initiating the BLA for DTX401, for the potential treatment of GSDIa, is an important milestone for this much needed treatment option for individuals and families affected by this disorder. Currently, patients are required to take large and frequent doses of cornstarch to protect themselves from the risk of potentially life-threatening hypoglycemia,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “By granting a rolling review, the FDA can begin reviewing the non-clinical 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.”

The BLA for DTX401 includes the previously disclosed 96-week data from the randomized, placebo-controlled Phase 3 study that demonstrated patients had even greater reductions in total daily cornstarch at their last visit compared to baseline in both the ongoing DTX401 group (-60%) and the Crossover Placebo to DTX401 group (-64%) when compared to the 48-week data. 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.

About DTX401

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. DTX401 is 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. DTX401 has been granted orphan drug designation, regenerative medicine advanced therapy (RMAT) designation and Fast Track designation from the U.S. FDA, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency.

About Glycogen Storage Disease Type Ia (GSDIa)

GSDIa is a serious inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies. GSDIa is estimated to affect approximately 6,000 people in commercially accessible geographies.

About Ultragenyx

Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

For more information on Ultragenyx, please visit the company's website at: .

Forward-Looking Statements and Use of Digital Media

Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, business plans and objectives for DTX401, expectations regarding the tolerability and safety of DTX401, expectations regarding the adequacy of clinical data to support the marketing application and approval of DTX401, the company’s intent to file, and potential timing and success of, the marketing application and other regulatory approvals for DTX401, expectations regarding timing of BLA submission and receiving potential approval of DTX401, expectations regarding the prevalence of patients of DTX401, future regulatory interactions, expectations regarding the company’s ability to resolve with the FDA the observations in the complete response letter, and the value to be generated by DTX401, and future clinical and regulatory developments for DTX401 are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop DTX401, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, the company’s limited experience in operating its own manufacturing facility, the ability of the company and its third party manufacturers to comply with regulatory requirements, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.

For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 6, 2025, and its subsequent periodic reports filed with the SEC. 

In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website () and LinkedIn website ().

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