DTX301: Gene therapy for the potential treatment of ornithine transcarbamylase (OTC) deficiency
Stage: Phase 3
Disease: OTC deficiency
Prevalence: 10,000 people in our territories
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 is one of six enzymes and two transporters that make up the urea cycle and breaks down ammonia into urea that can be excreted from the body. Ammonia is a potent neurotoxin and even slightly elevated levels can lead to neurologic and cognitive signs and symptoms. Prolonged elevations in ammonia can lead to a metabolic crisis with progressive and irreversible neurocognitive damage with each crisis. Approximately 10,000 people in our territories have OTC deficiency. 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 establish normally functioning OTC enzyme and urea cycle to metabolize ammonia
DTX301 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of the OTC gene using a single intravenous infusion. Long term Phase 1/2 data demonstrate an acceptable safety profile and durable metabolic control and sustained responses. 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, EU and United Kingdom and Fast Track Designation in the United States.