Genglycos (pariglasgene brecaparvovec) / Ultragenyx - LARVOL DELTA

Phase 3 Randomized Trial Results of DTX401 AAV Gene Therapy for the Treatment of GSDIa. (PubMed, J Inherit Metab Dis) - "The DTX401 safety profile was acceptable, and expected hepatic reactions consisting of transaminase elevations were managed with prophylactic corticosteroids. Treatment with DTX401 resulted in both a statistically significant and clinically meaningful reduction in cornstarch intake in the 48-week PEAP versus placebo, with greater cornstarch reductions in both groups at Week 96."

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

Efficacy and nutritional changes from a phase 3 trial of DTX401 gene therapy for GSDIa (SSIEM 2026) - P3 | "DTX401 resulted in statistically significant cornstarch reductions at W48 post-treatment versus placebo, with greater cornstarch reductions in both groups at W96. As cornstarch was reduced after DTX401, non-cornstarch calories were increased to avoid unintentional energy deficits and to redistribute macronutrients toward a more balanced diet."

Clinical • Gene therapy • P3 data • Dyslipidemia • Gene Therapies • Hypertriglyceridemia • Hypoglycemia • Metabolic Disorders

Ultragenyx Pharmaceutical…announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval for GENGLYCOS (pariglasgene brecaparvovec-opnr), also known as DTX401, in adult and pediatric patients eight years and older with glycogen storage disease type Ia (GSDIa) (GlobeNewswire) - "GSDIa is an ultra-rare genetic metabolic disorder caused by a deficiency of the enzyme needed to release glucose from the liver to the bloodstream....The approval of GENGLYCOS is based on positive data from the 48-week randomized, double-blind, placebo-controlled Phase 3 GlucoGene study which treated 46 participants aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose) or placebo, showing a reduction in the cornstarch requirements in the treated group (p<0.001)."

FDA approval • Genetic Disorders • Metabolic Disorders • Rare Diseases

Management of acute infusion-related reactions in AAV gene therapy guided by mechanistic insight (ASGCT 2026) - "Methods IRRs were observed in two participants who received an AAV8 gene therapy (DTX401) for Glycogen Storage Disease Type Ia and in one participant who received an AAV9 gene therapy (UX701) for Wilson’s Disease. AAV gene therapy IRRs appear to be rate-related and possibly driven by complement activation, not IgE-mediated mechanisms. Conclusion The risk of IRRs can be mitigated by a slow, staged infusion, allowing successful administration of a therapeutic gene therapy dose."

Gene therapy • Gene Therapies • Hepatology • Immunology • Metabolic Disorders • Movement Disorders

Administration of AAV gene therapy in mice, non-human primates, and GSDIa patients with pre-existing anti-AAV8 antibodies (ASGCT 2026) - P3 | "The safety and efficacy in the five participants with anti-AAV8 antibodies prior to DTX401 administration (including the three with anti-AAV8 antibodies at dosing) were consistent with the overall DTX401-treated group. Conclusion Together, the mouse, cynomolgus macaque, and DTX401 clinical trial participant findings support the potential safety and efficacy of dosing GSDIa patients with low anti-AAV8 antibody titers."

Gene therapy • Preclinical • Gene Therapies

COMPARISON OF DAILY VS WEEKLY ADMINISTRATION FORMATS OF THE GLYCOGEN STORAGE DISEASE FUNCTIONAL ASSESSMENT DIARY (GSD FAD) (ISPOR 2026) - P3 | "It was developed as a daily eDiary in the DTX401-CL301 Phase 3, randomized, double-blind, placebo-controlled study investigating the efficacy and safety of DTX401 in individuals ≥8 years living with GSDIa (NCT05139316)... Results suggest that Daily and Weekly formats can be considered alternate forms and provide initial evidence to support the use of the Weekly GSD FAD version in research settings where the administration of a daily eDiary is not feasible."

Metabolic Disorders

PATIENT DESCRIPTIONS OF THE BENEFITS OF A REDUCED CORNSTARCH DOSE REGIMEN IN A PHASE 3 TRIAL OF DTX401 FOR GLYCOGEN STORAGE DISEASE TYPE IA (ISPOR 2026) - P3 | "Trial participants who reduced cornstarch dose frequency following DTX401 treatment commonly reported reduced regimen burden and associated improvements in quality of life."

Clinical • P3 data • Gene Therapies • Metabolic Disorders

PATIENT DESCRIPTIONS OF IMPROVED ABILITY TO SELF-REGULATE BLOOD SUGAR LEVELS IN A PHASE 3 TRIAL OF DTX401 FOR GLYCOGEN STORAGE DISEASE TYPE IA (ISPOR 2026) - P3 | "This research summarizes the lived experiences of symptom improvements in a trial from the perspective of individuals with GSDIa. Allowing trial participants to directly share their experiences, in addition to standard trial assessments, provides a unique opportunity to better understand the impact of DTX401 treatment."

Clinical • P3 data • Gene Therapies • Metabolic Disorders • Severe Hypoglycemia

Long-term Efficacy and Safety of DTX401, an AAV8-mediated, Liver-directed Gene Therapy, for the Treatment of GSDIa: Phase 1/2 End-of-Study Results (ACMG 2026) - P, P1/2 | "DTX401 demonstrated durability of treatment effect with sustained and persistent reductions in cornstarch for up to 6 years, as well as improved fasting tolerance and patient-perceived improvements in disease and treatment burden. Based on up to 6 years of follow-up post dosing, DTX401 also demonstrated an acceptable and manageable safety profile. The longer-term efficacy and safety of DTX401 will be evaluated in the GSDIa Disease Monitoring Program (NCT06636383)."

Clinical • Gene therapy • P1/2 data • Dyslipidemia • Gene Therapies • Hypertriglyceridemia • Hypoglycemia • Infectious Disease • Metabolic Disorders • Novel Coronavirus 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=49 | Completed | Sponsor: Ultragenyx Pharmaceutical Inc | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Metabolic Disorders

Ultragenyx Announces U.S. FDA Acceptance and Priority Review of the Biologics License Application (BLA) for DTX401 AAV Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa) (The Manila Times) - "The FDA granted the BLA Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) action date of August 23, 2026...The BLA is based on data from a rigorous clinical development program that includes 52 treated patients and up to six years of follow-up."

FDA filing • PDUFA • Priority review • Metabolic Disorders • Rare Diseases

Trial Interviews to Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy. (PubMed, J Health Econ Outcomes Res) - P1/2 | "Most interviewees in this open-label trial of investigational DTX401 described positive experiences, including substantial reduction in burden and improved health-related quality of life following treatment throughout the trial. To optimize patient outcomes and experience with gene therapy, guidance on and close monitoring of dietary changes during implementation should be provided."

Interview • Journal • Gene Therapies • Metabolic Disorders

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) (GlobeNewswire) - "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."

FDA filing • Gene Therapies • Genetic Disorders • Metabolic Disorders

Qualitative Trial Interviews to Explore the Experience of Adult and Pediatric Patients Participating in a Pivotal Phase 3 Trial of DTX401 for Glycogen Storage Disease Type Ia (ISPOR-EU 2025) - P3 | "During qualitative interviews, adult and pediatric Phase 3 trial participants described reduced treatment burden, improvements in GSDIa, and improved overall QoL following treatment with DTX401."

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

Ultragenyx Reports Third Quarter 2025 Financial Results and Corporate Update (GlobeNewswire) - "UX111 AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): expect to resubmit Biologics License Application (BLA) early in 2026....DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): BLA rolling submission underway, expect to complete in the fourth quarter of 2025."

FDA filing • Lysosomal Storage Diseases

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