FDA Clears Ultragenyx to Begin Clinical Trials of Gene Therapy for Glycogen Storage Disease Type Ia

April 23, 2018

Rare Daily Staff

The U.S. Food and Drug Administration gave Ultragenyx Pharmaceutical clearance to begin clinical trials of DTX401, an adeno-associated virus vector-based gene therapy for the treatment of glycogen storage disease type Ia, a genetic enzyme deficiency that result in the inability to regulate blood sugar.

GSDIa is the most common genetically inherited glycogen storage disease. It is caused by a defective gene for the enzyme glucose-6-phosphatase-α, resulting in the inability to regulate blood sugar.

Hypoglycemia in GSDIa patients 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 pharmacological therapies. An estimated 6,000 patients worldwide are affected by GSDIa.

DTX401 is an experiment adeno-associated virus vector type 8 gene therapy designed to deliver stable expression and activity of the deficient enzyme following 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. Regulatory agencies in the United States and Europe have granted DTX401 Orphan Drug designation.

“GSDIa is a devastating disease that requires patients to adhere to a strict and burdensome cornstarch feeding protocol to maintain normal blood glucose levels and prevent hypoglycemia,” said Emil Kakkis, CEO and president of Ultragenyx. “Failure of dietary therapy can lead to episodes of severe hypoglycemia resulting in seizures and death.”

The open-label, multicenter study will evaluate the safety, tolerability and therapeutic response of DTX401 in adults with GSDIa. Key efficacy assessments include time to hypoglycemia, impact on biomarkers such as lipids, uric acid, and measurement of glycogen in liver. There are three potential dosing cohorts in the study, and three patients will be enrolled in each cohort.

Enrollment in the phase 1/2 study is expected to begin in the first half of 2018, with data from the first cohort expected in the second half of 2018.

April 23, 2018
Photo: Emil Kakkis, CEO and president of Ultragenyx


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