Ultragenyx Reports Positive Results from First Cohort of Phase 1/2 Study Glycogen Storage Disease Gene Therapy

January 4, 2019

Rare Daily Staff

Ultragenyx Pharmaceutical reported positive topline safety and efficacy data from the first, lowest dose cohort of its ongoing phase 1/2 study of DTX401, a gene therapy for the treatment of glycogen storage disease type Ia (GSDIa), the most common genetically inherited glycogen storage disease.

GSDIa is caused by a defective gene for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar. Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies.

DTX401 is an investigational adeno-associated virus vector type 8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter. DTX401 is 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.

A biologic response, reflected by improved glucose control and increased time to hypoglycemia during fasting, was observed in all three patients in the study, with two patients demonstrating a clinically meaningful improvement in time to hypoglycemia during a controlled fasting challenge.

“We are very pleased with what we are seeing in this first cohort of patients. After 20 years of research in preparation for this study, it is extremely rewarding to see such positive results on the low dose,” said David Weinstein, professor and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and UConn Health. “We are excited about the potential as the dose is increased.”

As of the primary cutoff date of November 28, 2018, there have been no infusion-related adverse events and no treatment-related serious adverse events reported.

The independent Data Monitoring Committee has completed its review of week 12 data from Cohort 1 and has concluded that it is safe to proceed to the second dose cohort of the study. The first patient in the second dose cohort is expected to be dosed in January 2019, and Cohort 2 data are expected in mid-2019.

Regulators in the United States and Europe have granted Orphan Drug designation to DTX401.


January 4, 2019
Photo: David Weinstein, professor and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and UConn Health

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