Ultragenyx shares long-term phase 3 results for gene therapy in metabolic disorder

Ultragenyx Pharmaceutical announced positive longer-term results from its phase 3 study of its AAV gene therapy, DTX401, for the treatment of glycogen storage disease type Ia, a serious inherited disease that results in the inability to regulate blood sugar.

Previously reported 48-week data show that 20 patients treated with DTX401 experienced statistically significant and clinically meaningful reductions in daily cornstarch intake compared to placebo, while maintaining glycemic control. Now, at week 96, even greater reductions in cornstarch were observed with maintained low levels of hypoglycemia, improved levels of euglycemia, and improved fasting tolerance. At week 96, both the DTX401 group (n=20) and the crossover group (n=19) achieved a mean reduction in daily cornstarch intake of 61% from baseline.

“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,” said Eric Crombez, MD, chief medical officer at Ultragenyx.

DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon and cortisol. It’s administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression.

Ultragenyx initiated the rolling submission of its BLA seeking approval for DTX401in August, submitting the nonclinical and clinical modules to the agency with a plan to complete the full BLA including submission of the CMC module in the fourth quarter of 2025.