Ultragenyx announces longer-term result from DTX401 AAV gene therapy study

Ultragenyx (RARE) announced longer-term results from its Phase 3 study of DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia. Previously reported 48 Week data show that patients treated with DTX401 experienced statistically significant and clinically meaningful reductions in daily cornstarch intake compared to placebo, while maintaining glycemic control. At Week 96, even greater reductions in cornstarch were observed with maintained low levels of hypoglycemia, improved levels of euglycemia, and improved fasting tolerance. The data were presented at the International Congress of Inborn Errors of Metabolism 2025 in Kyoto, Japan. As previously reported, the study met its primary endpoint with patients treated with DTX401 experiencing a mean reduction in cornstarch of 41% at Week 48 compared to 10% reduction in the placebo group. Data at Week 96 showed even greater improvements, with both the DTX401 group and the crossover group achieving a mean reduction in daily cornstarch intake of 61% from baseline. Participants in both groups also experienced statistically significant improvements in other cornstarch-related endpoints. At Week 96, the DTX401 group saw an increased mean reduction in nighttime cornstarch of 70% and the crossover group saw a mean reduction of 75%. Two-thirds of participants across both groups eliminated at least one nighttime cornstarch dose following treatment with DTX401. Importantly, participants maintained low levels of hypoglycemia and improved levels in euglycemic range throughout the second year of the study despite substantial reductions in daily cornstarch intake. Participants dosed with DTX401 also experienced improved fasting tolerance in a controlled fasting challenge through year 2 of the study, demonstrating protection from severe hypoglycemia. At Week 96, 83% of the DTX401 group and 95% of the crossover group reported improvements in disease burden as measured by the Patient Global Impression of Change, a single item questionnaire that asked participants how their condition changed since the start of the study. Improvements in quality of life were further demonstrated through interviews with Phase 3 study participants. During Week 48 and Week 96 interviews, DTX401-treated participants most frequently reported reductions in cornstarch intake that, at the group level, exceeded the baseline-identified threshold for meaningful change; as well as less hypoglycemia and less tiredness-all of which were reported as treatment priorities in baseline interviews. The most frequently reported functional improvements at Week 48 and Week 96 included improvements in physical, social and diet/daily regimen impacts. The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. Anticipated hepatic reactions were manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity, malignancy or thrombotic microangiopathy were observed in the study through Week 96. Hypertriglyceridemia was observed in all study groups but more frequently following DTX401.