NOVATO, Calif., March 12, 2026 — Ultragenyx Pharmaceutical announced positive results from its Phase 3 Enh3ance clinical trial evaluating DTX301, an investigational AAV8 gene therapy for the treatment of ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder.
At Week 36, patients treated with DTX301 demonstrated a statistically significant 18% reduction in 24-hour plasma ammonia levels compared with placebo (p=0.018), meeting the study’s primary endpoint. Treated patients maintained ammonia levels within the normal range throughout the study period, representing a clinically meaningful improvement in metabolic control.
Among patients who entered the trial with abnormal ammonia levels despite strict diet and medication, eight of nine rapidly achieved normal ammonia levels after treatment, which were generally maintained through Week 36.
Beyond the primary endpoint, patients also reported meaningful clinical benefits. Assessments using the Patient Global Impression of Change (PGIC) showed that 71% of treated patients reported being “much improved” in overall OTC symptoms, compared with none in the placebo group. Improvements were also observed in disease symptoms and the impact of OTC deficiency on daily life.
DTX301 demonstrated a favorable safety profile consistent with previous clinical studies. The most common adverse events were mild to moderate transient liver reactions, which were managed with steroid treatment. One treatment-related serious adverse event involving acute hepatitis resolved with steroid therapy. Importantly, no adverse events related to thrombotic microangiopathy, malignancy, or severe immune reactions were reported.
Hyperammonemic crises requiring hospitalization occurred five times in the placebo group, including one death, compared with one event and no deaths in the treated group.
DTX301 (avalotcagene ontaparvovec) is a single-dose intravenous AAV8 gene therapy designed to deliver a functional copy of the OTC gene to liver cells, enabling sustained enzyme activity that helps the body detoxify ammonia. The therapy has received Orphan Drug designation in the U.S. and EU and Fast Track designation from the FDA.
The Enh3ance trial enrolled 37 patients across 16 clinical sites in 10 countries. The study will now continue to evaluate its second primary endpoint, which focuses on reducing treatment burden—such as reliance on ammonia scavenger medications and strict dietary protein restriction—through 64 weeks of follow-up. Additional data are expected in the first half of 2027.
OTC deficiency is caused by mutations in a liver enzyme responsible for ammonia detoxification. Excess ammonia can lead to life-threatening metabolic crises, neurological damage, and hospitalization. Current treatments rely on strict dietary management and lifelong medication but do not eliminate the risk of severe hyperammonemia.
The new findings highlight the potential of AAV gene therapy to directly address the underlying genetic cause of OTC deficiency and improve metabolic control for patients living with this rare disorder.
