pariglasgene brecaparvovec (DTX401) / Ultragenyx - LARVOL DELTA

Cross-reactive Immunologic Material (CRIM) Analyses for AAV Gene Therapy (ASGCT 2025) - P1/2 | "For individuals with OTC enrolled in the DTX301 Phase 1/2 study (ClinicalTrials.gov Identifier: NCT02991144), 1 of 8 participants with available data was characterized as CRIM-medium risk due to a hemizygous splicing mutation predicted to cause absence of a portion of ornithine transcarbamylase protein. For individuals with GSDIa enrolled in the DTX401 Phase 1/2 study (ClinicalTrials.gov Identifier: NCT03517085), two of 12 participants were characterized as CRIM-high risk and three of 12 were characterized as CRIM-medium risk due to homozygous or compound heterozygous mutations predicted to result in truncation or absence of glucose-6-phosphatase protein...As more people consider taking AAV gene therapy, understanding the impact of CRIM more comprehensively will help guide discussions to optimize these potentially transformative treatments. Disease Focus of Abstract:Rare Diseases"

Gene therapy • Gene Therapies • Immunology • Rare Diseases • CD4 • CD8 • HLA-B • HLA-C

The Seropositivity Dilemma for AAV Gene Therapy (ASGCT 2025) - "To explore the impact of seropositivity further, we characterized the total binding antibody titers in individuals with Ornithine Transcarbamylase Deficiency (OTC), Glycogen Storage Disease type Ia (GSDIa) and Wilson Disease (WD), as these are the populations that are under investigation for DTX301, DTX401 and UX701 AAV gene therapies, respectively. These data support further investigation into more frequent AAV TAb testing and will inform discussions about the possibility of dosing low TAb+ individuals in future AAV GT trials. Disease Focus of Abstract:Rare Diseases"

Gene therapy • Gene Therapies • Hepatology • Metabolic Disorders • Movement Disorders • Rare Diseases

Qualitative Interviews to Characterize Disease and Treatment Burden at Baseline in Adult and Pediatric Patients Participating in a Pivotal Phase 3 Trial of DTX401 for the Treatment of Glycogen Storage Disease Type Ia (ISPOR 2025) - P3 | "Qualitative within-trial interviews helped to demonstrate the substantial burden faced by patients with GSDIa and identify goals and expectations for treatment."

Clinical • Interview • P3 data • Gene Therapies • Hypoglycemia • Metabolic Disorders • Pediatrics

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) (ESPE-ESE 2025) - No abstract available

Clinical • Gene therapy • P3 data • Gene Therapies • Metabolic Disorders

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) (ESPE-ESE 2025) - P3 | "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)."

Clinical • Gene therapy • P3 data • Gene Therapies • Metabolic Disorders

Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa). (PubMed, J Inherit Metab Dis) - P1/2 | "DTX401 showed a favorable safety and efficacy profile at Week 52. Participants in all cohorts showed significant cornstarch need reductions from baseline to Week 52."

Journal • Gene Therapies • Hypoglycemia • Inflammation • Metabolic Disorders

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients with Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3 | N=49 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Metabolic Disorders

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients with Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3 | N=52 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Active, not recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Metabolic Disorders

Long-Term Efficacy and Safety in Adults with Glycogen Storage Disease Type IA (GSD IA) from a Phase 1/2 Clinical Trial and Long-Term Follow-Up Study of DTX401, an AAV8-Mediated, Liver-Directed Gene Therapy (ASGCT 2024) - P, P1/2 | "DTX401 showed efficacy and an acceptable safety profile in all treated participants at Week 52 that was durable and sustained for up to five years. Participants in all cohorts showed a significant reduction in cornstarch needs from baseline to both Week 52 and to the last available timepoint. Participants treated with DTX401 should continue to be monitored long-term for overall metabolic control."

Clinical • Gene therapy • P1/2 data • Dyslipidemia • Gastroenterology • Gene Therapies • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Renal Disease

Trial interviews to explore glycogen storage disease type Ia patient experiences of gene therapy (SIMD 2024) - P1/2 | "Background: As part of a Phase 1/2, open-label, safety and dose-finding study of DTX401 in adults with glycogen storage disease type Ia (GSDIa; NCT03517085), patient interviews were conducted at multiple timepoints after DTX401 gene therapy (GT) administration to characterize participant clinical trial experience, including impacts of GSDIa and GT effects on GSDIa symptoms, treatment satisfaction, and comparison of existing treatment to GT. Twelve participants (≥18 years) were enrolled, with three participants in each of four cohorts: Cohort 1: 2.0 × 1012 genome copies (GC)/kg with a reactive steroid regimen; Cohort 2: 6.0 × 1012 GC/kg with a reactive steroid regimen; Cohort 3: 6.0 × 1012 GC/kg with an optimized reactive steroid regimen; Cohort 4: 6.0 × 1012 GC/kg with a prophylactic steroid regimen... The majority of trial participants interviewed described positive experiences from GT, including substantial reduction in treatment burden and..."

Clinical • Gene therapy • Interview • Gene Therapies • Metabolic Disorders

Effects of DTX401 gene therapy administration on endocrine dysregulation in glycogen storage disease type Ia (SIMD 2024) - "Patients with GSD Ia display inappropriate cortisol responses to fasting hypoglycemia. Although the pathophysiology is not completely understood, both central and peripheral causes may contribute to this finding. After DTX401 administration, slow corrections of endocrine abnormalities were observed in some participants."

Gene therapy • Gene Therapies • Hypoglycemia • Metabolic Disorders

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3 | N=46 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Feb 2025 ➔ Dec 2025

Trial completion date • Gene Therapies • Metabolic Disorders

"First up Andrew Grimm for Ultragenyx GSDIa DTX401 Fully enrolled, 52 months complete. Now in LTFU. #ASGCT23" (@drecwalsh)

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3 | N=50 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Apr 2024 ➔ Feb 2025 | Trial primary completion date: Apr 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Gene Therapies • Metabolic Disorders

Efficacy and Safety at Week 52 and up to Four Years in Adults with Glycogen Storage Disease Type IA (GSDIa): Results from a Phase 1/2 Clinical Trial and Long-Term Follow-Up Study of DTX401, an AAV8-Mediated, Liver-Directed Gene Therapy (ASGCT 2023) - P=N/A, P1/2 | "DTX401 showed a positive efficacy and safety profile in all treated patients at Week 52 that was sustained for up to four years in patients enrolled in Cohort 1. Patients in all cohorts showed a significant reduction in cornstarch needs from baseline to both Week 52 and to the last available timepoint. All participants remain in the follow-up study and updated efficacy and safety results will be reported."

Clinical • Gene therapy • P1/2 data • Dyslipidemia • Gene Therapies • Hypertriglyceridemia • Metabolic Disorders • Renal Disease

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3 | N=50 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Metabolic Disorders

Sustained efficacy and safety up to 3.5 years in adults with glycogen storage disease type Ia (GSDIa): longer-term results from a phase 1/2 clinical trial of DTX401, an AAV8-mediated, liver-directed gene therapy (ESGCT 2022) - No abstract available

Clinical • P1/2 data • Gene Therapies • Metabolic Disorders

Sustained Efficacy and Safety at Week 52 and up to Three Years in Adults with Glycogen Storage Disease Type iA (GSDIa): Results from a Phase 1/2 Clinical Trial of DTX401, an AAV8-mediated, Liver-directed Gene Therapy (ASGCT 2022) - P1/2 | "DTX401 showed a positive efficacy and safety profile in all treated patients at Week 52 that was sustained for up to three years in patients enrolled in Cohort 1. Patients in all cohorts showed a significant reduction in cornstarch needs from baseline to both Week 52 and to the last available timepoint. Additional glycemic control, fasting time, and health-related quality of life data will be reported."

Clinical • P1/2 data • Gene Therapies • Metabolic Disorders

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P3; N=50; Recruiting; Sponsor: Ultragenyx Pharmaceutical Inc

Clinical • New P3 trial • Gene Therapies • Metabolic Disorders

Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P1/2; N=12; Completed; Sponsor: Ultragenyx Pharmaceutical Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gene Therapies • Metabolic Disorders

An Phase 3 clinical study comparing a vector transferring the gene for Glucose-6-Phosphatase with placebo in adults with Glycogen Storage Disease Type Ia. Een klinische fase 3-studie waarin een vector die het gen voor glucose-6-fosfatase overdraagt, wordt vergeleken met placebo bij volwassenen met glycogeenstapelingsziekte type Ia. (clinicaltrialsregister.eu) - P3; N=50; Sponsor: Ultragenyx Pharmaceutical Inc.

Clinical • New P3 trial • Gene Therapies • Genetic Disorders • Metabolic Disorders

[VIRTUAL] Longterm, sustained efficacy and safety from a phase 1/2 clinical trial of an AAV8mediated liverdirected gene therapy in adults with glycogen storage disease type Ia (ESGCT 2021) - P1/2 | "All unrelated SAEs were classified as serious due to hospitalizations; all resolved. DTX401 showed a positive and sustained longterm efficacy and safety profile in all treated patients, in favor of the 6.0x10 12 GC/kg dose (dose by ddPCR 1.0x10 13 GC/kg) as the optimal biological dose for a pivotal phase 3 trial expected to start in the second half of 2021."

Clinical • P1/2 data • Gene Therapies • Metabolic Disorders

A clinical study to learn about the effects of a virus that transfers the gene for Glucose- 6-Phosphatase (G6Pase) in adults with Glycogen Storage Disease Type Ia Un ensayo clínico para aprender los efectos del virus que transfiere el gen de la glucosa-6-fosfatasa (G6Pasa) en adultos con glucogenosis de tipo Ia (clinicaltrialsregister.eu) - P1/2; N=12; Ongoing; Sponsor: Ultragenyx Pharmaceutical Inc.

Clinical • New P1/2 trial • Gene Therapies • Genetic Disorders • Metabolic Disorders

[VIRTUAL] AAV8-Mediated Liver-Directed Gene Therapy as a Potential Therapeutic Option in Adults with Glycogen Storage Disease Type Ia (GSDIa): Updated Phase 1/2 Clinical Trial Results (ASGCT 2021) - P1/2 | "DTX401 had an acceptable safety profile and sustained improvement in biological G6Pase activity to Week 52 in the nine subjects from Cohorts 1 through 3, with a significant reduction in total daily cornstarch intake. Percentage of time spent in euglycemia increased, and in most subjects, body weight decreased. Subjects also reported increased quality of life across a range of measures."

Clinical • P1/2 data • Gene Therapies • Metabolic Disorders • Severe Hypoglycemia

Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa) (clinicaltrials.gov) - P1/2; N=12; Active, not recruiting; Sponsor: Ultragenyx Pharmaceutical Inc; Recruiting ➔ Active, not recruiting; N=18 ➔ 12

Clinical • Enrollment change • Enrollment closed • Gene Therapies • Metabolic Disorders