Ultragenyx Reports Positive Phase 3 Results for DTX401 in GSDIa Gene Therapy Study

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has announced positive topline results from their Phase 3 GlucoGene study (NCT05139316). This study evaluated the efficacy of DTX401, an investigational gene therapy, for treating individuals aged eight and older with glycogen storage disease type Ia (GSDIa). The results indicate significant progress in managing this rare genetic disorder.

The study's primary endpoint was met, demonstrating that DTX401 significantly reduced daily cornstarch intake compared to a placebo at Week 48. The mean reduction in the DTX401 group was 41.3%, while the placebo group only showed a 10.3% reduction. This finding is statistically significant and clinically relevant. Dr. Eric Crombez, Chief Medical Officer at Ultragenyx, highlighted the importance of these results, noting that the data aligns with earlier Phase 1/2 studies and underscores the therapy's capability to aid in glycogen breakdown for endogenous glucose production in the liver.

Secondary endpoints were also achieved, including a reduction in the number of daily cornstarch doses and the maintenance of glucose control at the 48-week mark. Specifically, patients in the DTX401 group experienced a reduction of 1.1 cornstarch doses per day, compared to a 0.2 dose reduction in the placebo group. Improvements were also seen in nighttime cornstarch dosing frequency and quantity. This double-blind study confirmed non-inferiority in glucose control compared to the placebo.

The Patient Global Impression of Change (PGIC) metric at Week 48 showed a median score of 2.0 (moderately improved) for the DTX401 group, compared to 1.0 (minimally improved) for the placebo group. Importantly, a PGIC score of moderately or higher improvement correlated with a reduction in total daily cornstarch intake by 30% or more, indicating this as a meaningful threshold for patients' clinical improvement.

Dr. Rebecca Riba-Wolman, study investigator and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center, emphasized that the significant reduction in cornstarch intake while maintaining glucose control could greatly benefit patients, enhancing their daily quality of life. GSDIa is a relentless disease that requires constant vigilance to prevent severe low blood sugar and acidosis, particularly during nighttime.

The safety profile of DTX401 was consistent with previous Phase 1/2 studies, with no serious adverse effects related to the treatment. Hepatic effects induced by the vector were manageable with prophylactic corticosteroids, and there were no observations of dorsal root ganglion toxicity or thrombotic microangiopathy up to Week 48.

Ultragenyx plans to present the full 48-week data at an upcoming scientific conference and will discuss these findings with regulatory authorities to support a marketing application in 2025. Previous long-term data from the Phase 1/2 study showed sustained reductions in cornstarch intake for up to five years, with a mean total daily reduction of 72%.

The Phase 3 study involved 46 patients who were randomized to receive either DTX401 or a placebo. After 48 weeks, eligible patients crossed over to the alternate treatment and will be followed for another 96 weeks. Upon completion, patients may enroll in a Disease Monitoring Program (DMP) for long-term follow-up of at least 10 years post-DTX401 infusion.

GSDIa is a severe genetic disorder caused by a defective gene encoding the enzyme G6Pase-α, leading to an inability to regulate blood glucose levels. Untreated, it can result in severe complications, including lactic acidosis, renal failure, and potentially death during infancy or childhood. Approximately 6,000 people worldwide are affected by GSDIa.

DTX401 is designed to deliver stable G6Pase-α expression in liver cells, helping to manage glucose levels effectively. The therapy has received several designations from the U.S. FDA and the European Medicines Agency, underscoring its potential as a breakthrough treatment for GSDIa.

Ultragenyx is focused on developing innovative treatments for rare genetic diseases, with a commitment to efficiently bringing effective therapies to patients in need. The company leverages its expertise in rare disease therapeutics to develop a robust pipeline of potential treatments.

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