DTX301
for OTC
DTX301 (avalotcagene ontaparvovec): Gene therapy for the potential treatment of ornithine transcarbamylase (OTC) deficiency
Program overview
Stage: Phase 3
Disease: OTC deficiency
Prevalence: 10,000 people in commercially accessible geographies
Disease Mechanism: Genetic defect in ammonia metabolism
Symptoms: Accumulating and irreversible neurocognitive damage
Treatment Modality: AAV8 gene therapy
Treatment Mechanism: Deliver transgene to produce normally functioning OTC enzyme
OTC deficiency: Inability of urea cycle to metabolize ammonia leads to neurocognitive damage
OTC deficiency, the most common urea cycle disorder, is caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. OTC deficiency is defined by acute hyperammonemic episodes, caused by excessive amounts of ammonia in the blood, that have a profound impact on patients’ health and quality of life, and can lead to hospitalization, cognitive and neurologic impairments, and death. Current management includes a strict diet that limits protein, and ammonia scavenger medications, which provide an alternate pathway for ammonia elimination. Current treatment may improve hyperammonemia but does not completely eliminate the risk of serious hyperammonemic crises as well as the risk of catastrophic outcomes. Many patients still have elevated excursions of their ammonia levels when evaluated over a 24-hour cycle period. Approximately 10,000 people in commercially accessible geographies have OTC deficiency, of whom approximately 80% are classified as late-onset and represent a clinical spectrum of disease severity. In the late-onset form of the disease, elevated ammonia can lead to significant medical issues for patients. 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.
Evaluating DTX301 to establish normally functioning OTC enzyme and urea cycle to metabolize ammonia
DTX301 (avalotcagene ontaparvovec) is an investigational AAV8 gene therapy designed to deliver stable expression and activity of the OTC gene using a single intravenous infusion. The Phase 3 Enh3ance study is underway 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 and EU and Fast Track Designation in the United States.