Ultragenyx's Glycogen Storage Disease Gene Therapy DTX401 Continues to Enable Decreases in Reductions in Daily Cornstarch Intake at 96 Weeks

Ultragenyx has reported that in the phase 3 GlucoGene clinical trial (NCT05139316), patients treated with DTX401, an investigational adeno-associated virus serotype 8 (AAV8) vector-based gene therapy that is intended to treat Glycogen Storage Disease Type Ia (GSDIa), showed even greater reductions in daily cornstarch intake at 96 weeks posttreatment compared to at 48 weeks posttreatment.¹ 

In comparison to previously reported 48-week data, the 96-week data showed that patients in both the ongoing DTX401 group and the crossover placebo to DTX401 group had greater reductions in their total daily cornstarch intake at their most recent visit compared to baseline. Specifically, the ongoing DTX401 group (n=20) and crossover group (n=19) together showed a 61% reduction from baseline at 96 weeks. Furthermore, patients in the DTX401 group achieved a 70% mean reduction in nighttime cornstarch intake and patients in the crossover group achieved a 75% mean reduction in nighttime cornstarch intake. Ultragenyx highlighted that across both these groups, 2 out of 3 patients were able to completely eliminate 1 or more nighttime cornstarch dose in the posttreatment period.

The company also noted that during the study’s second year, hypoglycemia stayed at low levels in the treated patients. In addition, levels in the euglycemic range (70-120 mg/dL) were improved. In a controlled fasting challenge protection from severe hypoglycemia (< 54 mg/dL) was also observed in treated patients through the study’s second year.

“In the second year of treatment, patients were able to further reduce cornstarch intake while continuing to maintain good glucose control," Eric Crombez, MD, the chief medical officer at Ultragenyx, said in a statement.¹ “These results are consistent with the positive data observed in the phase 1/2 study and underscore the robustness and progressive improvement of treatment effect that can potentially be achieved with this gene therapy. The ability to reduce dependence on cornstarch reflects the establishment of the liver’s ability to break down glycogen to produce glucose during times of fasting or metabolic stress. This ability to regulate glucose levels has reduced the burden of disease and potential threat of severe or fatal hypoglycemia for these patients.”

Ultragenyx also reported that +1 to +3 improvements in disease burden, as assessed by the Patient Global Impression of Change questionnaire, were reported by 83% of patients in the DTX401 group and 95% of patients in the crossover group at 96 weeks posttreatment. Interviews were also conducted for the treated patients at 48 weeks and 96 weeks posttreatment, and improvements in physical, social, and diet/daily regimen impacts constituted the most frequently reported functional improvements. Lessened hypoglycemia and lessened tiredness were also reported.

With regard to safety, DTX401’s safety profile was characterized as “acceptable and expected” and consistent with data from the earlier phase 1/2 results. As of 96 weeks posttreatment, there were no AAV8 class effects of dorsal root ganglion toxicity, malignancy, or thrombotic microangiopathy and the anticipated hepatic reactions were able to be managed with prophylactic corticosteroids. All groups in the GlucoGene trial, including the control group, showed cases of hypertriglyceridemia, but these were more frequently seen in patients who had been treated with DTX401.

Alongside the main GlucoGene results reported above, Ultragenyx also announced findings from an open-label Japanese cohort that included 3 patients aged 8 to 17 years. At 24 weeks posttreatment, this cohort showed a 95% mean reduction in daily cornstarch intake from baseline. Furthermore, 2 of the patients discontinued daily cornstarch entirely by 24 weeks posttreatment and the other patient discontinued daily cornstarch entirely by 36 weeks posttreatment. Across the 3 patients, glycemic control was improved or sustained, lower levels of hypoglycemia were observed, and euglycemia was improved. There were no serious adverse events reported in the group.

Notably, in August 2025, Ultragenyx began the submission of a rolling biologics license application (BLA) to the FDA for DTX401.² The company stated that the nonclinical and clinical modules have been submitted, and the chemistry, manufacturing, and controls information will be submitted later. Ultragenyx anticipates that the full BLA will be submitted in the fourth quarter of this year. The BLA is supported by 96-week data from GlucoGene.

REFERENCES
1. Ultragenyx announces positive longer-term data from phase 3 study of DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. September 8, 2025. Accessed September 16, 2025. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-positive-longer-term-data-phase-3-study
2. Ultragenyx initiates rolling submission of biologics license application (BLA) to U.S. FDA for DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). News release. Ultragenyx Pharmaceutical Inc. August 18, 2025. Accessed September 16, 2025. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-initiates-rolling-submission-biologics-license