ECEESPE2025 Rapid Communications Rapid Communications 3: Metabolism and Aging (6 abstracts)
Efficacy and safety results from a pivotal phase 3 trial of DTX401, an AAV8-mediated liver-directed gene therapy, in individuals with glycogen storage disease type Ia (GSDIa)
John Mitchell 1 , Jose Abdenur 2 , Foekje de Boer 3 , Monica Boyer 2 , Margo Breilyn 4 , Nicola Pierri 5 , María Couce 6 , Terry Derks 3 , Areeg El-Gharbawy 7 , Diva De Leon 8 , Karen Loechner 9 , Nicola Longo 10 , Allan Lund 11 , Miguel Angel Martinez Olmos 6 , Shawn McCandless 12 , Bibiana Mello de Oliveira 13 , Malaya Mount 9 , Helen Mundy 14 , Nicole Muschol 15 , Ruben Overduin 3 , Kadakkal Radhakrishnan 16 , Rebecca Riba-Wolman 9 , David Rodriguez-Buritica 17 , Alessandro La Rosa 18 , Katalin Ross 8 , Alessandro Rossi 5 , Heather Saavedra 17 , René Santer 15 , Brian Shayota 10 , G. Peter Smit 3 , Carolina M de Souza 13 , Mary Sowa 2 , David Weinstein 9 , Joseph Wolfsdorf 19 , Anne Blake 20 , Deepali Mitragotri 20 , Richard Collis 20 & Andrew Grimm 20
1Montreal Children’s Hospital, Montreal, Canada; 2Children’s Hospital of Orange County, Orange, United States; 3Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; 4Mount Sinai, New York, United States; 5Department of Translational Medicine, University of Naples Federico II, Naples, Italy; 6Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; 7Duke University, Durham, United States; 8Children’s Hospital of Philadelphia, Philadelphia, United States; 9University of Connecticut, Farmington, United States; 10University of Utah, Salt Lake City, United States; 11Centre for Inherited Metabolic Diseases, Rigshospitalet, Copenhagen, Denmark; 12Children’s Hospital Colorado, Aurora, United States; 13Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; 14Metabolic Service, Evelina London Children’s Hospital, London, United Kingdom; 15University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 16Cleveland Clinic, Cleveland, United States; 17Department of Pediatrics, Division of Medical Genetics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth Houston) and Children’s Memorial Hermann Hospital, Houston, United States; 18Istituto Giannina Gaslini, Genova, Italy; 19Boston Children’s Hospital, Boston, United States; 20Ultragenyx Pharmaceutical Inc., Novato, United States
JOINT3352
Background: GSDIa is a rare, potentially life-threatening inborn error of carbohydrate metabolism caused by biallelic G6PC pathogenic variants, resulting in glucose-6-phosphatase deficiency. DTX401 is an investigational adeno-associated virus serotype 8 vector containing the human G6PC gene.
Methods: DTX401-CL301 (GlucoGene Study; ClinicalTrials.gov: NCT05139316), is an ongoing, pivotal, phase 3, double-blind, randomized, placebo-controlled trial in patients ≥8 years old with GSDIa. Participants were randomly assigned (1:1) to receive blinded DTX401 or placebo. At Week 48, participants entered a 48-week Crossover Period when, in a blinded manner, those randomized to DTX401 received placebo and placebo received DTX401. The primary endpoint was change from Baseline to Week 48 in daily cornstarch intake, DTX401 versus placebo.
Results: The study met the primary endpoint: at Week 48, the Primary Efficacy Analysis Period (PEAP), DTX401 treatment resulted in a mean (standard deviation [SD]) daily cornstarch intake reduction of 41.0% (18.4) versus a 10.1% (18.0) reduction with placebo; P <0.0001 based on mixed model of repeated measures. In the Crossover Period, greater reductions in total daily cornstarch were observed in both the ongoing DTX401 group and the Crossover Placebo to DTX401 group (Table). Glycemic control was maintained in participants treated with DTX401 despite significant reductions in daily cornstarch intake. Patient experience data support cornstarch reduction clinical meaningfulness, with Week 48 Patient Global Impression of Change Moderately or Much Improved corresponding to a 34% mean reduction in daily cornstarch intake. Anticipated vector-induced liver enzyme elevations were manageable with prophylactic corticosteroids. Elevations in triglycerides were observed in individual participants, requiring adjustments of cornstarch and dietary intake.
| Week 96 | ||||
| Mean (SD) | n | DTX401 | n | Crossover Placebo to DTX401* |
| Daily cornstarch, % change from baseline | 13 | -60.9 (18.9) | 13 | -64.7 (24.9) |
| Nighttime cornstarch, % change from baseline | 12 | -66.1 (33.5) | 10 | -74.2 (26.5) |
| Percent glucose values <70 mg/dl, change from baseline | 17 | 3.78 (4.96) | 16 | 2.33 (3.23) |
| Percent glucose values <54 mg/dl, change from baseline | 17 | 0.85 (0.88) | 16 | 0.27 (0.47) |
| *Data at 48 weeks after DTX401 treatment | ||||
Conclusion: Treatment with DTX401 resulted in statistically significant and clinically meaningful reductions in cornstarch intake in the 48-week PEAP versus placebo. Greater reductions in cornstarch were observed in both groups in the Crossover Period after Week 48. Experience with disease management post-gene therapy and confidence that all participants had been treated with DTX401 likely contributed to improvements in the Crossover Period (Year 2) versus the PEAP (Year 1). DTX401 had an acceptable safety profile.
Volume 110
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more