Ultragenyx publishes 96-week Phase 3 data for GENGLYCOS in GSDIa
Ultragenyx Pharmaceutical has published full 96-week data from its Phase 3 GlucoGene study of GENGLYCOS (pariglasgene brecaparvovec-opnr) in glycogen storage disease type Ia (GSDIa), with results appearing in The Journal of Inherited Metabolic Disease. The FDA-approved AAV gene therapy, also known as DTX401, met its primary endpoint at Week 48 and continued to show deepening benefit through the second year of follow-up.
Both the original treatment group (n=20) and the crossover group (n=19) achieved a mean 61% reduction in daily cornstarch intake from baseline by Week 96, up from the 41% reduction recorded in the DTX401 arm at the primary analysis. Crucially, participants maintained glycaemic control throughout, with low rates of hypoglycaemia and improved time in the euglycaemic range of 70 to 120 mg/dL despite substantially reduced cornstarch supplementation.
Nighttime burden and patient-reported outcomes
The publication places particular emphasis on nighttime dosing, which the authors describe as among the most burdensome aspects of current GSDIa management. By Week 96, a third of participants in the original DTX401 group and 42% of the crossover group had completely eliminated overnight cornstarch dosing while maintaining glycaemic control. At Week 48, that proportion stood at 50% for those who had eliminated at least one nighttime dose, compared with 7% in the placebo group (p=0.031).
Patient-reported outcomes reinforce the clinical picture. At baseline, participants defined a meaningful reduction in cornstarch as around 45% per day. By Week 48, 83% of DTX401-treated participants had met or exceeded their own threshold, rising to 95% of crossover participants and 83% of the original group by Week 96. The release also notes that cornstarch accounted for nearly half of participants' total caloric intake before treatment; following therapy, dietary composition shifted toward a more balanced, food-based pattern.
Lead author Dr John Mitchell, a paediatric endocrinologist at the Montreal Children's Hospital and investigator on the study, said the reduction in overnight dosing "will have the most meaningful impact by reducing sleep disruption," and described long-term outcomes from the 96-week period as "particularly important, offering valuable insight into how post-treatment management may continue to evolve."
Regulatory and competitive context
GENGLYCOS received FDA approval under the accelerated approval pathway for patients aged eight and older with GSDIa. Continued approval remains contingent on confirmatory trial data, and Ultragenyx has enrolled participants in a 10-year Disease Monitoring Programme following study completion. The accelerated approval designation means the agency could revisit the label if longer-term benefit is not confirmed, a risk the company acknowledges in its forward-looking disclosures.
GSDIa affects an estimated 1,500 to 2,500 patients in the United States and 6,000 to 8,000 across commercially accessible geographies worldwide, making it an ultra-rare indication. The gene therapy space for metabolic liver diseases remains relatively uncrowded compared with more competitive rare-disease categories such as haemophilia, where multiple approved products compete directly. Ultragenyx's nearest-term challenge is demonstrating durable real-world outcomes as GENGLYCOS transitions from a controlled trial setting to clinical practice, where patient selection and post-infusion management protocols may differ from the study conditions. The safety profile was consistent with previously reported findings; the most common treatment-related adverse events were transient liver enzyme elevations managed with prophylactic corticosteroids, and no cases of dorsal root ganglion toxicity or thrombotic microangiopathy were observed through Week 96.