DTX301: AAV8 Gene Therapy for Ornithine Transcarbamylase (OTC) Deficiency

OTC deficiency: the most common urea cycle disorder

OTC deficiency is part of the urea cycle, an enzymatic pathway in the liver that converts excess nitrogen, in the form of ammonia, to urea for excretion. This type of deficiency leads to increased levels of the neurotoxin ammonia. Patients with OTC deficiency suffer from acute hyperammonemic episodes that can lead to hospitalization, adverse cognitive and neurologic effects, and death. Approximately 10,000 people in the developed world have OTC deficiency, of whom approximately 80% are classified as late-onset, our target population. Approved therapies, which must be taken multiple times a day over a lifetime, do not eliminate the risk of future metabolic crises. Currently, the only curative approach for OTC is liver transplantation.

Evaluating DTX301 to prevent or reduce the occurrence of complications associated with OTC deficiency

DTX301 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of the OTC gene using a single intravenous infusion. Data from the three dose cohorts in an ongoing Phase 1/2 clinical study of DTX301 demonstrated an acceptable initial safety profile and evidence of clinical activity. Specifically, six of the nine dosed patients responded, including all three patients who received the highest dose. Ultragenyx plans to conduct a Phase 3 clinical study to evaluate the effect of DTX301 on ammonia and its ability to reduce patients’ need for ammonia scavenger medication and a protein-restricted diet, the current standard of care.

DTX301 was granted Orphan Drug Designation in the United States, EU and United Kingdom and Fast Track Designation in the United States.

Learn more about DTX301 clinical studies