Ultragenyx Completes Dosing of First Cohort in Study of Gene Therapy in OTC Deficiency

November 16, 2017

Rare Daily Staff

Ultragenyx Pharmaceutical said it has completed patient dosing in the first cohort of three patients enrolled in a phase 1/2 study of DTX301, a gene therapy for the treatment of ornithine transcarbamylase deficiency, a urea cycle disorder.

OTC deficiency is caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. People with OTC deficiency can build up excessive levels of ammonia in their blood, potentially resulting in acute and chronic neurological deficits and other toxicities.

More than 10,000 people are affected by OTC deficiency worldwide, of which approximately 80 percent are classified as late-onset. In the late onset form of the disease, elevated ammonia can lead to significant medical issues for patients who are in need of new disease-modifying therapies. Neonatal onset disease occurs in males, presents as severe disease, and can be fatal at an early age.

Approved therapies, which must be taken multiple times a day for the patient’s entire life, do not eliminate the risk of future metabolic crises. Currently, the only curative approach is liver transplantation.

DTX301 is an investigational AAV type 8 gene therapy designed to deliver stable expression and activity of OTC following a single intravenous infusion and has been shown in preclinical studies to normalize levels of urinary orotic acid, a marker of ammonia metabolism.

The phase 1/2 clinical study is an open-label, dose-finding and safety study of single ascending doses of DTX301 in adults with late-onset OTC Deficiency who are clinically stable and under good metabolic control at time of dosing. To evaluate therapeutic response of DTX301, the study measures the change in the rate of ureagenesis, the pathway for the metabolism of ammonia which is deficient in OTC patients. Ammonia levels, neurocognitive assessment, biomarkers, and safety will also be evaluated.

The decision to proceed to the next, higher dose cohort will be made after the data monitoring committee evaluates the safety data for all patients in the previous dosing cohort.

Regulatory authorities in the United States and Europe have granted Ultragenyx Orphan Drug Designation for DTX301.

Initial data from this first cohort of three patients is expected in early 2018. 

November 16, 2017

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