FDA Clears IND Application for New Gene Therapy

This morning, it was announced by Ultragenyx Pharmaceutical Inc. that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for DTX401 for the treatment of glycogen storage disease type Ia (GSDIa).

DTX401 is being developed as an adeno-associated virus (AAV) vector based type 8 gene therapy, and is intended to deliver stable expression and activity of the enzyme glucose-6-phosphatase-α (G6Pase-α) following a single intravenous infusion.

A defective gene in the G6Pase-α enzyme is the leading cause of all cases of GSDIa, the most common genetically inherited glycogen storage disease. The mutation can cause an inability to regular blood sugar, or glucose, and severe hypoglycemia. In individuals with GSDIa, hypoglycemia can be life-threatening. The accumulation of the complex sugar glycogen in certain organs and tissues can damage tissues and their ability to function normally.

“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. Failure of dietary therapy can lead to episodes of severe hypoglycemia resulting in seizures and death,” said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx in a press release. “We look forward to initiating our clinical program for DTX401, our gene therapy designed to replace the deficient enzyme in the liver to improve glucose control and prevent the devastating short and long-term consequences of this disease.”

An open-label, multicenter Phase 1/2 study of the gene therapy is expected to begin in the first half of 2018, and 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 3 potential dosing cohorts in the study, and 3 patients will be enrolled in each cohort.

Data from the first cohort expected in the second half of 2018.

In previous preclinical studies, DTX401 has been shown to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. As of this writing, there are no approved pharmacological therapies intended for GSDia, and approximately 6,000 patients are affected by it worldwide.

DTX401 has been granted Orphan Drug Designation in both the United States and Europe.

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