Ultragenyx Announces Positive Longer-term Data from Phase 3 Study of DTX401 AAV Gene Therapy for the Treatment of Glycogen Storage Disease Type Ia (GSDIa)
Ultragenyx Pharmaceutical (NASDAQ: RARE) announced positive 96-week results from its Phase 3 study of DTX401, a gene therapy for glycogen storage disease type Ia (GSDIa). The therapy demonstrated significant improvements in reducing cornstarch dependency while maintaining glycemic control.
Key findings at Week 96 include a 61% mean reduction in daily cornstarch intake for both treatment and crossover groups, with 70-75% reduction in nighttime cornstarch usage. Two-thirds of participants eliminated at least one nighttime dose. The therapy's efficacy was further validated by data from a Japanese cohort, where all three pediatric participants achieved 95% reduction in cornstarch intake by Week 24, with complete elimination in all cases.
Patient quality of life improved significantly, with 83-95% of participants reporting reduced disease burden. The treatment demonstrated an acceptable safety profile with manageable hepatic reactions.
Ultragenyx Pharmaceutical (NASDAQ: RARE) ha annunciato risultati positivi a 96 settimane dal suo studio di Fase 3 su DTX401, una terapia genica per la glicogenosi di tipo Ia (GSDIa). La terapia ha mostrato miglioramenti significativi nella riduzione della dipendenza dall'amido di mais mantenendo il controllo glicemico.
I principali risultati alla settimana 96 includono una riduzione media del 61% nell'assunzione giornaliera di amido di mais sia nei gruppi trattati sia in quelli crossover, con una riduzione del 70-75% nell'uso notturno. Due terzi dei partecipanti hanno eliminato almeno una dose notturna. L'efficacia è stata confermata anche da dati di una coorte giapponese, in cui tutti e tre i pazienti pediatrici hanno raggiunto una riduzione del 95% dell'assunzione di amido di mais entro la settimana 24, con eliminazione completa in tutti i casi.
La qualità di vita dei pazienti è migliorata significativamente, con il 83-95% dei partecipanti che ha riportato una riduzione del carico della malattia. Il trattamento ha mostrato un profilo di sicurezza accettabile con reazioni epatiche gestibili.
Ultragenyx Pharmaceutical (NASDAQ: RARE) anunció resultados positivos a las 96 semanas de su estudio de Fase 3 de DTX401, una terapia génica para la enfermedad de almacenamiento de glucógeno tipo Ia (GSDIa). La terapia demostró mejoras significativas al reducir la dependencia del almidón de maíz mientras mantenía el control glucémico.
Los hallazgos clave en la semana 96 incluyen una reducción media del 61% en la ingesta diaria de almidón de maíz tanto en los grupos tratados como en los de crossover, con una reducción del 70-75% en el uso nocturno. Dos tercios de los participantes eliminaron al menos una dosis nocturna. La eficacia se validó además con datos de una cohorte japonesa, donde los tres participantes pediátricos lograron una reducción del 95% en la ingesta de almidón de maíz en la semana 24, con eliminación completa en todos los casos.
La calidad de vida de los pacientes mejoró de forma significativa, con un 83-95% de los participantes reportando una menor carga de enfermedad. El tratamiento mostró un perfil de seguridad aceptable con reacciones hepáticas manejables.
Ultragenyx Pharmaceutical (NASDAQ: RARE)는 글리코겐 저장병 Ia형(GSDIa) 치료용 유전자치료제 DTX401에 대한 3상 연구의 96주차 긍정적 결과를 발표했습니다. 이 치료법은 혈당 조절을 유지하면서 옥수수전분 의존도를 유의하게 개선했습니다.
96주차 주요 결과는 치료군과 크로스오버군 모두에서 일일 옥수수전분 섭취량이 평균 61% 감소했으며, 야간 섭취는 70~75% 감소했습니다. 참가자의 3분의 2는 최소 한 번의 야간 복용을 중단했습니다. 일본 코호트 데이터에서도 효능이 검증되어, 소아 참가자 3명 모두가 24주차에 옥수수전분 섭취량을 95% 감소시켰고, 모두 완전 중단을 달성했습니다.
환자의 삶의 질도 크게 향상되어 참가자의 83-95%가 질병 부담 감소를 보고했습니다. 치료는 관리 가능한 간 반응을 동반한 허용 가능한 안전성 프로파일을 보였습니다.
Ultragenyx Pharmaceutical (NASDAQ: RARE) a annoncé des résultats positifs à 96 semaines de son essai de phase 3 sur DTX401, une thérapie génique pour la maladie de surcharge en glycogène de type Ia (GSDIa). La thérapie a montré des améliorations significatives en réduisant la dépendance à l'amidon de maïs tout en maintenant le contrôle glycémique.
Les résultats clés à la semaine 96 incluent une réduction moyenne de 61 % de la consommation quotidienne d'amidon de maïs pour les groupes traités et en crossover, avec une réduction de 70 à 75 % de l'utilisation nocturne. Les deux tiers des participants ont supprimé au moins une dose nocturne. L'efficacité a été confirmée par les données d'une cohorte japonaise, où les trois participants pédiatriques ont atteint une réduction de 95 % de la consommation d'amidon de maïs à la semaine 24, avec une élimination complète dans tous les cas.
La qualité de vie des patients s'est nettement améliorée, 83 à 95 % des participants déclarant une diminution de la charge de la maladie. Le traitement a présenté un profil de sécurité acceptable avec des réactions hépatiques gérables.
Ultragenyx Pharmaceutical (NASDAQ: RARE) gab positive 96-Wochen-Ergebnisse seiner Phase-3-Studie zu DTX401 bekannt, einer Gentherapie für die Glykogenspeicherkrankheit Typ Ia (GSDIa). Die Therapie zeigte signifikante Verbesserungen bei der Verringerung der Abhängigkeit von Maisstärke bei gleichzeitiger Aufrechterhaltung der glykämischen Kontrolle.
Wesentliche Befunde in Woche 96 beinhalten eine mittlere Reduktion der täglichen Maisstärkeaufnahme um 61% sowohl in den Behandlungs- als auch in den Crossover-Gruppen, mit einer 70–75%igen Reduktion des nächtlichen Verbrauchs. Zwei Drittel der Teilnehmer schafften es, mindestens eine nächtliche Dosis wegzulassen. Die Wirksamkeit wurde durch Daten einer japanischen Kohorte weiter bestätigt: Alle drei pädiatrischen Teilnehmer erreichten bis Woche 24 eine 95%ige Reduktion der Maisstärkeaufnahme und in allen Fällen eine vollständige Eliminierung.
Die Lebensqualität der Patienten verbesserte sich deutlich; 83–95% der Teilnehmer berichteten über eine verringerte Krankheitslast. Die Behandlung wies ein akzeptables Sicherheitsprofil mit handhabbaren Leberreaktionen auf.
- 61% mean reduction in daily cornstarch intake achieved at Week 96
- 70-75% reduction in nighttime cornstarch doses across treatment groups
- 95% reduction in cornstarch intake in Japanese cohort with complete elimination in all three patients
- 83-95% of patients reported improvements in disease burden
- Maintained glycemic control despite substantial cornstarch reductions
- Acceptable safety profile with no serious adverse events
- Higher frequency of hypertriglyceridemia observed in treatment groups
- Requires prophylactic corticosteroid regimen to manage hepatic reactions
Insights
Ultragenyx's DTX401 gene therapy shows durable 96-week efficacy for GSDIa, enabling 61% cornstarch reduction with maintained glycemic control.
The 96-week data from Ultragenyx's Phase 3 study of DTX401 gene therapy for Glycogen Storage Disease Type Ia (GSDIa) shows progressive improvements over the previously reported 48-week results. Patients achieved a
The efficacy extends beyond just cornstarch reduction - patients experienced a
The data demonstrates the therapy's mechanism is working as intended - restoring the liver's ability to break down glycogen and maintain glucose homeostasis during fasting. The improved fasting tolerance observed during controlled challenges provides evidence that DTX401 is addressing the fundamental metabolic defect in GSDIa.
Particularly compelling is the Japanese cohort data where all three pediatric patients completely eliminated cornstarch dependence - achieving what would be considered a functional cure. While this represents a small sample, it suggests potentially transformative efficacy, especially in younger patients.
The safety profile remains consistent with earlier studies, with manageable hepatic reactions controlled through prophylactic corticosteroids. Importantly, no concerning AAV8 vector-related safety signals emerged through 96 weeks of follow-up.
From an investment perspective, these 96-week results significantly strengthen Ultragenyx's DTX401 value proposition. The data shows durability of effect with increasing benefit over time - a crucial factor for gene therapies seeking regulatory approval and market adoption.
The
The Japanese cohort data showing complete cornstarch elimination in pediatric patients is particularly noteworthy, as it suggests potential for even stronger efficacy in certain populations. This could expand the addressable market and potentially command premium pricing if approved.
Quality-of-life improvements are substantial, with
The favorable safety profile with no unexpected adverse events through 96 weeks addresses a key risk factor for AAV gene therapies. Absence of dorsal root ganglion toxicity, malignancy concerns, or thrombotic microangiopathy that have affected other AAV programs is reassuring for the regulatory pathway.
With compelling efficacy, durable results, strong safety profile, and patient-reported benefits, DTX401 appears well-positioned for regulatory submission. If approved, it would represent Ultragenyx's first gene therapy to market and validate their platform technology for additional pipeline programs.
At Week 96 participants experienced even greater reductions in daily cornstarch intake while maintaining low levels of hypoglycemia, improved levels of euglycemia and improved fasting tolerance
Phase 3 results are further supported by early data from open-label Japanese cohort (n=3) where all participants were able to eliminate daily cornstarch while maintaining or improving glycemic control
DTX401 was well tolerated with an acceptable safety profile
NOVATO, Calif., Sept. 08, 2025 (GLOBE NEWSWIRE) -- Today, Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) announced positive longer-term results from its Phase 3 study of DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). Previously reported 48 Week data show that patients treated with DTX401 (n=20) experienced statistically significant and clinically meaningful reductions in daily cornstarch intake compared to placebo, while maintaining glycemic control. At Week 96, even greater reductions in cornstarch were observed with maintained low levels of hypoglycemia, improved levels of euglycemia, and improved fasting tolerance. The data were presented at the International Congress of Inborn Errors of Metabolism (ICIEM) 2025 in Kyoto, Japan.
“In the second year of treatment, patients were able to further reduce cornstarch intake while continuing to maintain good glucose control. These results are consistent with the positive data observed in the Phase 1/2 study and underscore the robustness and progressive improvement of treatment effect that can potentially be achieved with this gene therapy,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “The ability to reduce dependence on cornstarch reflects the establishment of the liver’s ability to break down glycogen to produce glucose during times of fasting or metabolic stress. This ability to regulate glucose levels has reduced the burden of disease and potential threat of severe or fatal hypoglycemia for these patients.”
Participants achieved statistically significant and clinically meaningful reductions in cornstarch while maintaining glycemic control
As previously reported, the study met its primary endpoint with patients treated with DTX401 (n=20) experiencing a mean reduction in cornstarch of
At Week 96, the DTX401 group saw an increased mean reduction in nighttime cornstarch of
Dr. John Mitchell, scientist in the Child Health and Human Development Program at the Research Institute of the McGill University Health Centre, pediatric endocrinologist at the Montreal Children’s Hospital, and an investigator on the study said: “The current treatment for GSDIa with multiple doses of uncooked cornstarch provides a heavy burden for individuals with this disease and requires continuous vigilance to prevent hypoglycemia. At present, there is no treatment that addresses the underlying cause and there is a clear unmet need for patients for a disease modifying therapy. Treatment with DTX401 resulted in an impressive reduction of both cornstarch quantity and dosing frequency while maintaining glucose levels in the target range. Treated individuals had less reliance on cornstarch with normalization of mealtimes. However, for me, the most significant result from the study is the reduction in the number of cornstarch doses overnight. Uninterrupted sleep leads to improvement in quality of life and less fatigue for patients and their families. This has important implications for the GSD population at large.”
Clinical benefits translated to improvements in patient-reported quality of life
At Week 96,
Improvements in quality of life were further demonstrated through interviews with Phase 3 study participants. During Week 48 and Week 96 interviews, DTX401-treated participants most frequently reported reductions in cornstarch intake that, at the group level, exceeded the baseline-identified threshold for meaningful change; as well as less hypoglycemia and less tiredness—all of which were reported as treatment priorities in baseline interviews. The most frequently reported functional improvements at Week 48 and Week 96 included improvements in physical, social and diet/daily regimen impacts.
DTX401 well tolerated with an acceptable safety profile
The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. Anticipated hepatic reactions were manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity, malignancy or thrombotic microangiopathy were observed in the study through Week 96. Hypertriglyceridemia was observed in all study groups but more frequently following DTX401.
Results further supported by data from three participants treated in open-label arm in Japan
The Phase 3 data is further supported by early results from all participants (n=3, all were pediatric ages 8-17 yo) treated with DTX401 in an open-label cohort that demonstrated a mean reduction in daily cornstarch intake of
About the Phase 3 GlucoGene study
The 48-week randomized, double-blind, placebo-controlled study treated 46 participants aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose measured by ddPCR) or placebo. There were 44 participants in the modified intention-to-treat (mITT) population providing efficacy data within the Week 48 analysis period following treatment with DTX401 (n=20) or placebo (n=24). At Week 48, eligible participants crossed over and received the alternate treatment. After crossover, participants will be followed for an additional 96 weeks. After study completion, participants will be offered enrollment into the GSDIa Disease Monitoring Program (DMP) where they will be followed for at least 10 years post-DTX401 infusion.
About DTX401
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 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 rare, serious, and life-threatening disease due to an inborn error of carbohydrate metabolism caused by pathogenic variants of the G6PC gene which encodes the enzyme 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 Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, 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.
Ultragenyx 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, our intent to file, and potential timing and success of, the marketing application and other regulatory approvals for DTX401, expectations regarding timing of receiving potential approval of DTX401, expectations regarding the prevalence of patients of DTX401, future regulatory interactions, 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, the risk that results from earlier studies may not be predictive of future study results, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, 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
Investors
Joshua Higa
ir@ultragenyx.com
Media
Jess Rowlands
media@ultragenyx.com
FAQ
What were the key results from Ultragenyx's (RARE) Phase 3 DTX401 gene therapy trial at 96 weeks?
How effective was DTX401 gene therapy in the Japanese cohort of GSDIa patients?
What safety concerns were identified in Ultragenyx's DTX401 Phase 3 trial?
How did DTX401 gene therapy impact patient quality of life in the Phase 3 trial?
What is the significance of cornstarch reduction in GSDIa treatment?
