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)
Ultragenyx Pharmaceutical (NASDAQ: RARE) has initiated a rolling submission of a Biologics License Application (BLA) to the FDA for DTX401, their AAV gene therapy treatment for Glycogen Storage Disease Type Ia (GSDIa). The company has submitted the non-clinical and clinical modules and plans to complete the full BLA with the chemistry, manufacturing and controls (CMC) module in Q4 2025.
The BLA includes 96-week Phase 3 study data showing significant cornstarch reduction in patients: 60% reduction in the ongoing DTX401 group and 64% reduction in the Crossover Placebo to DTX401 group. The submission will address FDA observations from the UX111 complete response letter regarding CMC and manufacturing facilities.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha avviato una submission rolling di una Biologics License Application (BLA) alla FDA per DTX401, la sua terapia genica AAV per la Malattia da Accumulo di Glicogeno di tipo Ia (GSDIa). L'azienda ha già inviato i moduli non clinici e clinici e prevede di completare la BLA completa con il modulo relativo a chimica, produzione e controlli (CMC) nel Q4 2025.
La BLA contiene i dati dello studio di Fase 3 a 96 settimane, che mostrano una significativa riduzione dell'assunzione di amido di mais: 60% di riduzione nel gruppo in trattamento continuativo con DTX401 e 64% di riduzione nel gruppo passato da placebo a DTX401. La submission risponderà alle osservazioni della FDA contenute nella lettera di complete response UX111 relative a CMC e strutture produttive.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha iniciado una presentación rolling de una Biologics License Application (BLA) ante la FDA para DTX401, su terapia génica con AAV para la Enfermedad de Almacenamiento de Glucógeno tipo Ia (GSDIa). La compañía ya ha remitido los módulos no clínicos y clínicos y planea completar la BLA completa con el módulo de química, fabricación y controles (CMC) en el Q4 2025.
La BLA incluye datos del estudio de Fase 3 a 96 semanas que muestran una reducción significativa del consumo de almidón de maíz: 60% de reducción en el grupo en curso con DTX401 y 64% de reducción en el grupo que cruzó de placebo a DTX401. La presentación abordará las observaciones de la FDA de la carta de respuesta completa UX111 relacionadas con CMC e instalaciones de fabricación.
Ultragenyx Pharmaceutical (NASDAQ: RARE)은(는) GSDIa(글리코겐 저장병 Ia형) 치료를 위한 AAV 유전자치료제 DTX401에 대해 FDA에 생물의약품 제조판매허가(BLA)의 롤링 제출을 시작했습니다. 회사는 비임상 및 임상 모듈을 제출했으며, 화학·제조·관리(CMC) 모듈을 포함한 전체 BLA를 2025년 4분기(Q4 2025)에 완료할 계획입니다.
BLA에는 96주간의 3상 연구 데이터가 포함되어 있으며, 환자의 옥수수전분 섭취가 크게 감소한 것으로 나타났습니다: 지속적으로 DTX401을 투여한 군에서 60% 감소, 위약에서 DTX401로 전환한 군에서 64% 감소를 보였습니다. 제출 자료는 CMC 및 제조 시설과 관련한 UX111 완전응답서(FDA)의 지적사항에 대응할 예정입니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a lancé une soumission progressive (rolling submission) d'une Biologics License Application (BLA) à la FDA pour DTX401, sa thérapie génique AAV pour la maladie de surcharge en glycogène de type Ia (GSDIa). La société a déposé les modules non cliniques et cliniques et prévoit de compléter la BLA complète avec le module chimie, fabrication et contrôles (CMC) au T4 2025.
La BLA comprend des données de l'étude de phase 3 sur 96 semaines montrant une réduction significative de la consommation d'amidon de maïs chez les patients : réduction de 60 % dans le groupe traité en continu par DTX401 et réduction de 64 % dans le groupe passant du placebo à DTX401. Le dossier répondra aux remarques de la FDA contenues dans la lettre de réponse complète UX111 concernant le CMC et les installations de fabrication.
Ultragenyx Pharmaceutical (NASDAQ: RARE) hat eine Rolling-Submission einer Biologics License Application (BLA) bei der FDA für DTX401, ihre AAV-Gentherapie für Glykogenspeicherkrankheit Typ Ia (GSDIa), eingeleitet. Das Unternehmen hat die nicht-klinischen und klinischen Module eingereicht und plant, die vollständige BLA mit dem Modul zu Chemie, Herstellung und Kontrollen (CMC) im Q4 2025 zu vervollständigen.
Die BLA enthält Daten einer 96-wöchigen Phase-3-Studie, die eine deutliche Reduktion der Maissirup-/Maisstärkeaufnahme bei Patienten zeigen: 60% Reduktion in der fortlaufenden DTX401-Gruppe und 64% Reduktion in der Gruppe, die von Placebo zu DTX401 wechselte. Die Einreichung wird die von der FDA im UX111-Complete-Response-Schreiben aufgeführten Hinweise zu CMC und Produktionsanlagen adressieren.
- Phase 3 trial showed significant 60-64% reduction in daily cornstarch requirements
- FDA granted rolling review, allowing earlier assessment of non-clinical and clinical data
- Potential first-in-class gene therapy treatment for GSDIa patients
- Previous FDA observations regarding CMC and manufacturing facilities need to be addressed
- Full BLA submission delayed until Q4 2025 pending CMC module completion
Insights
Ultragenyx's BLA submission for DTX401 gene therapy marks significant regulatory progress for GSDIa treatment, with strong Phase 3 efficacy data.
Ultragenyx has initiated a rolling BLA submission to the FDA for DTX401, their AAV gene therapy targeting Glycogen Storage Disease Type Ia (GSDIa). This regulatory strategy allows the FDA to begin reviewing the submitted non-clinical and clinical modules while Ultragenyx completes the chemistry, manufacturing and controls (CMC) module expected in Q4 2025.
The submission includes impressive 96-week Phase 3 data showing
Notably, Ultragenyx is proactively addressing potential regulatory hurdles by incorporating lessons learned from their UX111 program, which previously received a complete response letter from the FDA. They're specifically working to resolve manufacturing facility observations that could otherwise delay approval. This demonstrates regulatory sophistication and increases 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.
Company expects to complete BLA submission in the fourth quarter of 2025
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 (-
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: 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 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).
Ultragenyx Contacts
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Joshua Higa
ir@ultragenyx.com
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FAQ
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