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

Rhea-AI Summary

Ultragenyx (NASDAQ: RARE) completed the rolling submission of its Biologics License Application to the U.S. FDA for DTX401 (pariglasgene brecaparvovec), an AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa), on Dec 30, 2025. The BLA includes non‑clinical, clinical, and completed chemistry, manufacturing, and controls (CMC) modules.

The submission is supported by a clinical program of 52 treated patients with up to six years follow‑up and Phase 3 GlucoGene randomized, double‑blind, placebo‑controlled data showing significant reductions in daily cornstarch intake, maintained low hypoglycemia, improved euglycemia, improved fasting tolerance, and patient‑reported quality‑of‑life benefits; DTX401 was reported as well tolerated with an acceptable safety profile.

Positive

• BLA submission to FDA completed on Dec 30, 2025
• Clinical program includes 52 treated patients
• Up to 6 years of follow‑up data submitted
• Phase 3 randomized data show reduced cornstarch intake
• Reported improved euglycemia and fasting tolerance
• Patient‑reported quality‑of‑life improvements (PGIC)

Negative

• Clinical dataset limited to 52 treated patients
• Regulatory approval is pending following FDA review

Key Figures

Treated patients 52 patients DTX401 clinical development program supporting BLA

Follow-up duration Up to six years Long‑term follow‑up in DTX401 development program

Market Reality Check

$23.21 Last Close

Volume Volume 21,272,267 vs 20‑day average 2,516,470 (relative volume 8.45x) shows unusually heavy trading ahead of this filing update. high

Technical Price $19.72 sits well below the $33.39 200‑day MA and near the $18.41 52‑week low, far from the $46.50 52‑week high.

Peers on Argus

While RARE moved sharply with a -42.32% decline, close biotech peers showed only modest mixed moves (e.g., TLX -1.01%, SRRK -1.25%, NAMS +0.34%), indicating stock‑specific dynamics rather than a broad sector move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 29	Phase 3 results	Negative	-42.3%	Setrusumab Phase 3 trials missed primary fracture endpoints, prompting sharp selloff.
Dec 19	Inducement grants	Neutral	+3.7%	RSU inducement awards to new hires under Nasdaq rule with standard four‑year vesting.
Nov 24	Investor conferences	Neutral	+2.3%	Announcement of CMO participation in December healthcare investor conferences.
Nov 21	Inducement grants	Neutral	-2.4%	Additional RSU inducement grants to new hires with four‑year vesting schedule.
Nov 04	Q3 earnings	Positive	-3.0%	Q3 revenue growth, royalty monetization and reaffirmed guidance met with a price decline.

Pattern Detected

RARE has reacted strongly to pivotal clinical setbacks, while routine corporate or conference news has produced modest moves. One recent earnings update with positive elements saw a negative price reaction, suggesting occasional divergence from fundamentally positive headlines.

Recent Company History

Over the last two months, Ultragenyx has balanced financial updates with major clinical developments. On Nov 4, 2025, it reported Q3 revenue of $159.9M, up 15% year‑over‑year, alongside a net loss of $180.4M and reaffirmed $640M–$670M 2025 revenue guidance. Routine items such as inducement RSU grants and investor conference participation led to only small price moves. In contrast, the Dec 29, 2025 Phase 3 setrusumab results, which missed primary fracture endpoints despite BMD gains, coincided with a sharp selloff. Today’s positive BLA completion for DTX401 arrives immediately after that setback.

Market Pulse Summary

This announcement marks completion of the rolling BLA for DTX401, an AAV gene therapy for GSDIa, backed by data from 52 treated patients and up to six years of follow‑up. Phase 3 results showed reduced cornstarch requirements, maintained glycemic control, and improved patient‑reported outcomes, with an acceptable safety profile. In the broader context of recent mixed clinical and financial news, investors may focus on the FDA review process, safety durability, and how DTX401 could reshape Ultragenyx’s future revenue mix.

Key Terms

biologics license application regulatory

"completed the rolling submission of its Biologics License Application (BLA) to the U.S."

A biologics license application is a formal request submitted to regulatory authorities seeking approval to market a new biological medicine, such as vaccines or treatments made from living organisms. It is a comprehensive review process that evaluates the safety, effectiveness, and manufacturing quality of the product. For investors, receiving approval signals that a biological therapy can be sold to the public, potentially leading to revenue growth and market success.

aav gene therapy medical

"DTX401 AAV gene therapy (pariglasgene brecaparvovec) as a treatment for"

AAV gene therapy uses a harmless adeno-associated virus as a delivery vehicle to carry a working copy of a gene into a patient’s cells, like a targeted mail carrier delivering a new instruction manual to fix a malfunctioning part. It matters to investors because these treatments can be one-time or long-lasting cures, driving high potential revenue and valuation but also carrying large development costs, regulatory hurdles and safety and manufacturing risks that affect returns.

glycogen storage disease type ia medical

"gene therapy ... as a treatment for Glycogen Storage Disease Type Ia (GSDIa)."

An inherited metabolic disorder in which the body cannot release stored sugar (glycogen) into usable glucose because a key enzyme is missing or not working, causing low blood sugar, enlarged liver, and other complications. For investors this matters because it creates a small but urgent market for treatments and diagnostics—successful drugs, gene therapies, or regulatory approvals can materially change a company’s prospects and valuation due to high medical need and limited existing options.

randomized, double-blind, placebo-controlled medical

"data from the randomized, double-blind, placebo-controlled Phase 3 GlucoGene study"

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

patient global impression of change medical

"quality of life, as measured by the Patient Global Impression of Change (PGIC) scale."

A patient global impression of change is a simple, patient-reported rating that asks whether a person’s overall health or symptoms have gotten better, worse, or stayed the same after treatment. For investors, it matters because this kind of direct feedback can influence regulators’ and doctors’ views of a therapy’s real-world benefit and therefore affect approval prospects, prescribing behavior and market acceptance — think of it as customer satisfaction for a medical treatment.

chemistry, manufacturing, and controls regulatory

"completed the package through submission of the chemistry, manufacturing, and controls (CMC) module."

Chemistry, manufacturing, and controls (CMC) is the detailed documentation of how a drug or medical product is made, tested, and kept consistent — like a recipe, factory checklist, and quality-control plan combined. Investors care because strong CMC means regulators are more likely to approve the product and the company can reliably scale production, while weak or incomplete CMC raises the risk of approval delays, production problems, extra costs, or recalls.

AI-generated analysis. Not financial advice.

If approved, DTX401 will be the first therapy approved to treat the underlying cause of GSDIa

NOVATO, Calif., Dec. 30, 2025 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that it has completed the rolling submission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA), seeking approval for DTX401 AAV gene therapy (pariglasgene brecaparvovec) as a treatment for Glycogen Storage Disease Type Ia (GSDIa).

"The completion of our rolling submission of the BLA for DTX401 is a significant step toward our commitment to deliver the first therapy that directly targets the underlying cause of GSDIa," said Eric Crombez, M.D., Chief Medical Officer at Ultragenyx. "Despite burdensome daily dietary and cornstarch management, patients continue to face life-threatening risks from acute hypoglycemia and chronic complications impacting the liver, kidneys, gastrointestinal system, bones, and growth. We look forward to continuing our collaboration with the FDA throughout the review process to be able to provide this potentially life-changing therapy to as many people living with GSDIa as possible.”

The BLA for DTX401 is based on data from a rigorous clinical development program that includes 52 treated patients and up to six years of follow-up. Previously announced data from the randomized, double-blind, placebo-controlled Phase 3 GlucoGene study demonstrate that patients treated with DTX401 experienced significant and clinically meaningful reductions in both the quantity and frequency of daily cornstarch intake while maintaining low levels of hypoglycemia, improved levels of euglycemia, and improved fasting tolerance. These clinical benefits translated to meaningful improvements in patient-reported quality of life, as measured by the Patient Global Impression of Change (PGIC) scale. DTX401 was well tolerated, with an acceptable safety profile.

The company was previously granted rolling review and submitted the non-clinical and clinical modules to the FDA in August; and has now completed the package through submission of the chemistry, manufacturing, and controls (CMC) module.

About DTX401 (pariglasgene brecaparvovec)
DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin and cortisol. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted Rare Pediatric Disease designation, orphan drug designation, Fast Track designation, and regenerative medicine advanced therapy (RMAT) designation from the U.S. FDA, as well as orphan drug and PRIority MEdicines (PRIME) designations from the European Medicines Agency.

About Glycogen Storage Disease Type Ia (GSDIa)
GSDIa is a rare, serious, and life-threatening disease due to an inborn error of carbohydrate metabolism caused by pathogenic variants of the G6PC gene which encodes G6Pase, an enzyme that is critical for the release of glucose from glycogen and other metabolic sources. Deficiency of G6Pase results in severe hypoglycemia during periods of fasting between meals and during the night along with excess hepatic glycogen storage, metabolic derangements and other disease related complications. Cornstarch is critical in the management of GSDIa throughout the day and night in providing an exogenous source of glucose to avoid sudden and severe drops in plasma glucose levels however current management strategies carry a significant burden to patients and families. 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: www.ultragenyx.com.

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 November 5, 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).

Ultragenyx Contacts

Investors
Joshua Higa
ir@ultragenyx.com

Media
Jess Rowlands
media@ultragenyx.com

FAQ

What did Ultragenyx (RARE) submit to the FDA on December 30, 2025?

Ultragenyx completed the rolling BLA submission for DTX401, including non‑clinical, clinical, and CMC modules.

How large is the clinical dataset supporting DTX401 (RARE)?

The submission is based on a program with 52 treated patients and up to six years of follow‑up.

What Phase 3 results support DTX401 for GSDIa (RARE)?

Phase 3 GlucoGene randomized data showed significant reductions in daily cornstarch intake with maintained low hypoglycemia and improved euglycemia.

Does the DTX401 filing include manufacturing data for RARE?

Yes; the company completed the BLA package with submission of the CMC module.

What safety outcomes were reported for DTX401 in the RARE submission?

DTX401 was reported as well tolerated with an acceptable safety profile in the submitted program.

Is FDA approval of DTX401 (RARE) guaranteed after the rolling submission?

No; the filing starts FDA review, and approval is pending following the agency's assessment.