Ultragenyx Reports Positive Phase 3 Data for Gene Therapy in Metabolic Disorder.

Ultragenyx Pharmaceutical reported long-term phase 3 data for gene therapy DTX401 in patients with glycogen storage disease type Ia (GSDIa). The data showed greater reductions in cornstarch with low levels of hypoglycemia compared to week 48 data.

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has announced positive longer-term data from its Phase 3 study of DTX401 AAV gene therapy for the treatment of glycogen storage disease type Ia (GSDIa). The company presented the results at the International Congress of Inborn Errors of Metabolism (ICIEM) 2025 in Kyoto, Japan.

The study, known as the GlucoGene study, involved 46 participants aged eight years and older, with 44 participants in the modified intention-to-treat (mITT) population providing efficacy data within the Week 48 analysis period. Participants were treated with DTX401 (n=20) or placebo (n=24). At Week 48, eligible participants crossed over and received the alternate treatment, followed by an additional 96 weeks of observation.

The results at Week 96 showed even greater reductions in daily cornstarch intake compared to the previously reported Week 48 data. The DTX401 group (n=20) and the crossover group (n=19) achieved a mean reduction in daily cornstarch intake of 61% from baseline, with participants in both groups experiencing 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.

Participants maintained low levels of hypoglycemia and improved levels in the euglycemic range (70-120 mg/dL) throughout the second year of the study despite substantial reductions in daily cornstarch intake. They also experienced improved fasting tolerance in a controlled fasting challenge (CFC) through year 2 of the study, demonstrating protection from severe hypoglycemia ( 54 mg/dL).

Clinical benefits translated to improvements in patient-reported quality of life. At Week 96, 83% of the DTX401 group and 95% of the crossover group reported improvements in disease burden (+1 to +3 change) as measured by the Patient Global Impression of Change (PGIC) questionnaire.

The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. No serious adverse events were reported, and the treatment was well tolerated.

The Phase 3 data are further supported by early results from an open-label arm in Japan, where three participants treated with DTX401 were able to eliminate daily cornstarch entirely and maintain or improve glycemic control.

About Glycogen Storage Disease Type Ia (GSDIa)
GSDIa is a rare, serious, and life-threatening disease due to an inborn error of carbohydrate metabolism caused by pathogenic variants of the G6PC gene. It affects approximately 6,000 people in commercially accessible geographies and currently has no approved pharmacologic therapies.

About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment.

References:
[1] https://www.marketscreener.com/news/ultragenyx-announces-positive-longer-term-data-from-phase-3-study-of-dtx401-aav-gene-therapy-for-the-ce7d59dfd988fe26
[2] https://www.morningstar.com/news/globe-newswire/9525154/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