Ultragenyx Publishes 96-Week GENGLYCOS Gene Therapy Data for Glycogen Storage Disease

Ultragenyx published 96-week results from its Phase 3 GlucoGene study of GENGLYCOS (pariglasgene brecaparvovec-opnr, also known as DTX401), an AAV8 gene therapy for glycogen storage disease type Ia (GSDIa), in The Journal of Inherited Metabolic Disease.¹ The randomized, double-blind, placebo-controlled study enrolled 46 participants aged eight and older; at Week 48, DTX401-treated participants achieved a mean 41% reduction in daily cornstarch intake compared with a 10% reduction in the placebo group (p<0.0001), meeting the study's primary endpoint.² Eligible participants then crossed over to receive the alternate treatment. By Week 96, both the original treatment group and the crossover group had reached a mean 61% reduction in daily cornstarch intake from baseline, with 67% to 72% of participants across both groups achieving at least a 50% reduction.²

How did the therapy affect nighttime treatment burden?

Among participants who required nighttime cornstarch dosing at baseline, 50% of DTX401-treated participants eliminated at least one nighttime dose by Week 48, compared with 7% of the placebo group (p=0.031).² By Week 96, 67% of participants in both groups had eliminated at least one nighttime dose, and 33% of the original treatment group and 42% of the crossover group had eliminated nighttime cornstarch dosing entirely.² Across the study population, participants maintained glycemic control in the euglycemic range of 70 to 120 mg/dL throughout the second year of the study despite these reductions.²

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, lead author of the publication, and an investigator on the study, said, "These results demonstrate the potential of gene therapy to provide greater stability in day-to-day life for patients with GSDIa and may help guard against the risk of severe hypoglycemia associated with missed doses of raw cornstarch. For me, the reduction in overnight cornstarch dosing will have the most meaningful impact by reducing sleep disruption, with patient-reported outcomes included in the publication underscoring the profound impact that cornstarch reductions may have on daily life."¹

Why does long-term durability matter for this class of gene therapy?

GENGLYCOS is built on an AAV8 vector, a delivery platform whose central appeal for chronic, lifelong conditions like GSDIa is durability. As BioPharm International has reported, AAV vectors are non-pathogenic to humans and have low immunogenicity, and can mediate long-term expression of a therapeutic gene, "an important factor when treating chronic conditions that require sustained gene expression," according to Emmanuelle Cameau, strategic technology partnership leader, Genomic Medicine, at Cytiva.³ GENGLYCOS received FDA accelerated approval on August 19, 2026 — six weeks before this longer-term data was published — based on reduction in daily cornstarch intake.⁴

What did Ultragenyx say about the significance of the data?

Eric Crombez, M.D., chief medical officer at Ultragenyx, said, "The complete results from this phase 3 study more fully capture the benefits of this gene therapy and the importance of providing patients the ability to breakdown glycogen to provide a source of glucose during fasting or times of increased metabolic demands. Most patients achieved cornstarch reductions that met or exceeded their own expectations, with substantially less overnight treatment burden and reduced dependence on the around-the-clock cornstarch need that defines life with this disease. Importantly, reducing cornstarch dependence while maintaining glycemic control indicates the establishment of the liver's ability to regulate glucose production on its own, giving us confidence that the therapy is directly addressing the underlying cause of disease and offering protection from the risk of life-threatening hypoglycemia."¹

What about safety?

The authors reported an acceptable and manageable safety profile through Week 96, consistent with earlier findings.¹ The most common treatment-related adverse events were transient elevations in liver enzymes, generally nonserious and managed with prophylactic corticosteroids.¹ No AAV8 class effects — dorsal root ganglion toxicity, malignancy, or thrombotic microangiopathy — were observed through Week 96, though hypertriglyceridemia occurred more frequently following DTX401 treatment than in the placebo group.¹ Because GENGLYCOS holds accelerated approval based on cornstarch-intake reduction, continued approval may depend on confirmatory verification of clinical benefit; participants completing the study will be offered enrollment in a 10-year post-infusion disease monitoring program.¹

What happens next?

Further analyses from the GlucoGene study are planned at Week 144, alongside the long-term monitoring program.¹

References

1. Ultragenyx Pharmaceutical Inc. Ultragenyx Announces the Publication of a Successful 96-Week Randomized, Placebo-Controlled Trial with Crossover Treatment of GENGLYCOS™ (also known as DTX401) AAV Gene Therapy in GSDIa in The Journal of Inherited Metabolic Disease. Press release. Published September 1, 2026. Accessed September 2, 2026.
2. Mitchell JJ, Abdenur JE, Collis RJI. Phase 3 Randomized Trial Results of DTX401 AAV Gene Therapy for the Treatment of GSDIa. Journal of Inherited Metabolic Disease, 2026 Sep;49(5):e70241. DOI: 10.1002/jimd.70241
3. Comparing Viral Vectors for Gene Therapy Delivery. BioPharm International. Published August 8, 2024. Accessed September 2, 2026.
4. Ultragenyx Pharmaceutical Inc. Ultragenyx Announces U.S. FDA Approval of GENGLYCOS™ Gene Therapy, the First-Ever FDA-Approved Treatment Designed to Treat the Underlying Cause of Glycogen Storage Disease Type Ia (GSDIa). Press release. Published August 19, 2026. Accessed September 2, 2026.