Ultragenyx Pharmaceutical has announced positive topline results from the Phase III Enh3ance trial of its investigational AAV8 gene therapy, avalotcagene ontaparvovec, for ornithine transcarbamylase (OTC) deficiency. The study demonstrated that a single infusion of the candidate significantly reduced ammonia levels in the blood over 24 hours and allowed patients to reduce their dependence on ammonia-scavenger medications and dietary protein restrictions while maintaining ammonia homeostasis. OTC deficiency is the most common urea cycle disorder, where the accumulation of ammonia can lead to severe neurological damage and death.

Avalotcagene ontaparvovec is the most advanced gene therapy candidate for OTC deficiency, designed to deliver a functional copy of the OTC gene to liver cells. The trial's 36-week data showed a statistically significant 18% reduction in plasma ammonia levels in treated patients compared to the placebo group, with 89% of patients with abnormal baseline levels achieving and sustaining normal levels. The therapy was well-tolerated, with no new safety signals beyond the known, manageable risk of transient liver enzyme elevation. The study continues, with full 64-week data expected in H1 2027.

PharmCube's NextBiopharm® database shows that gene therapy is the most commonly used drug modality to target OTC. Click here to request a free trial for NextBiopharm®.