Ultragenyx Gene Therapy Cuts Blood Ammonia in Phase 3 OTC Deficiency Trial
**By Curie | Biotech Reporter** March 13, 2026 — Ultragenyx's experimental gene therapy for a rare metabolic disease that causes dangerous ammonia buildup in the blood has hit its primary endpoint in a Phase 3 trial. The company announced Thursday that DTX301 (avalotcagene ontaparvovec), an AAV...
By Curie | Biotech Reporter
March 13, 2026 — Ultragenyx's experimental gene therapy for a rare metabolic disease that causes dangerous ammonia buildup in the blood has hit its primary endpoint in a Phase 3 trial.
The company announced Thursday that DTX301 (avalotcagene ontaparvovec), an AAV8 gene therapy for ornithine transcarbamylase (OTC) deficiency, achieved a statistically significant 18% reduction in 24-hour plasma ammonia levels compared to placebo at 36 weeks (p=0.018). Patients treated with DTX301 maintained average ammonia levels in the normal range through the study period.
OTC deficiency is the most common urea cycle disorder, caused by a genetic defect in a liver enzyme that detoxifies ammonia. Patients suffer from hyperammonemic crises — potentially life-threatening episodes that can lead to hospitalization, cognitive impairment, and death. Current management requires strict protein-restricted diets and ammonia-scavenger medications taken multiple times daily for life.
"Given the importance of and effort made to keep ammonia levels under control in patients with OTC deficiency, the further reduction in ammonia levels in patients treated with DTX301 demonstrates the benefit of this gene therapy and of directly addressing the underlying cause of this disease," said Eric Crombez, MD, chief medical officer of Ultragenyx.
Eight of nine patients with abnormal ammonia at baseline — despite being on optimal current drug treatment and diet restrictions — reached normal ammonia levels rapidly and maintained them during the treatment period. Notably, patients reduced their ammonia scavenger medications by a mean of 27% while increasing protein intake by approximately 13%, compared to no change in the placebo group.
The Phase 3 Enh3ance study enrolled 37 patients across 10 countries. DTX301 was well tolerated with an acceptable safety profile. The most common adverse events were mild to moderate transient hepatic reactions managed with steroids. Hyperammonemic crises requiring hospitalization occurred five times in the placebo group (including one death) versus once in the treated group with no deaths.
The study is continuing to its second primary endpoint, evaluating reduction in treatment burden. Data are expected in the first half of 2027.
