Ultragenyx Pharmaceutical Inc. announced positive topline results from the Phase 3 GlucoGene study (NCT05139316) evaluating DTX401, an investigational gene therapy for the treatment of patients aged eight years and older with glycogen storage disease type Ia (GSDIa). The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p<0.0001).

Across patients treated with DTX401, the mean reduction in cornstarch continued to decline over the 48-week period. In the treatment group, all patients achieved a reduction in cornstarch, with 68% achieving =30% reduction and 37% achieving =50% reduction compared to the placebo group, which achieved the same reductions in 13% and 4% of patients, respectively, at Week 48. The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48.

Treatment with DTX401 resulted in a mean reduction of 1.1 cornstarch doses per day in the DTX401 treatment group compared with a mean reduction of 0.2 in the placebo group (p=0.0011). Patients in the DTX401 group also showed significant improvement in both frequency and quantity of nighttime cornstarch dosing compared with the placebo group. This blinded study established non-inferiority (p<0.0001) of glucose control between the study groups while the treatment group significantly reduced daily cornstarch intake.

The Patient Global Impression of Change (PGIC) at Week 48 showed a median score of 2.0 (moderately improved) for the DTX401 treatment group and 1.0 (minimally improved) for the placebo group (p=0.132). Moderately or higher improved PGIC scores correlated with a =30% reduction in total daily cornstarch intake indicating that this is a clinically meaningful threshold for patients. The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results.

Anticipated vector-induced hepatic effects were all non-serious and manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity or thrombotic microangiopathy were observed in the study through Week 48. Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year.

These results will be discussed with regulatory authorities to support a marketing application in 2025. Phase 1/2 Data Presented at American Society of Gene and Cell Therapy 2024: Ultragenyx recently presented long-term DTX401 Phase 1/2 data demonstrating durable response, with sustained, clinically meaningful reductions in cornstarch lasting up to 5 years in patients treated with open-label DTX401 as of the data cut-off. All 12 patients in the study have been followed for an average of 4 years and continue to demonstrate improved glucose control, with a mean total daily reduction of cornstarch intake of 72% (p<0.0001) from baseline to their last available timepoint.