An Ultragenyx gene therapy has scored a win at the midway point of its phase 3 trial, successfully reducing ammonia levels in patients with a rare urea cycle disorder.
Thirty-six weeks after one-time treatment with the AAV-based gene therapy DTX301, patients’ ammonia levels were 18% lower than placebo, a statistically significant result that met one of the trial’s co-primary endpoints, Ultragenyx reported March 12.
After meeting the measure for change in 24-hour plasma ammonia levels, the trial still must meet another primary endpoint—the percent of patients who achieve a response as measured by discontinuation or reduction in baseline disease management. That will be assessed 64 weeks after treatment.
The phase 3 trial has enrolled 37 patients with the rare genetic disease ornithine transcarbamylase (OTC) deficiency, which is the lack of a key enzyme for clearing ammonia from the blood. Ammonia is a natural byproduct of protein digestion, but, if it builds up too much in the body, it can become toxic.
DTX301 treatment kept patients’ ammonia levels at healthy levels even as patients stopped taking other medicines and increased the amount of protein in their diet, Eric Crombez, M.D., Ultragenyx’s chief medical officer, said in the release.
“We are extremely encouraged by these findings given the significant medical needs faced by patients with OTC deficiency, who remain at risk for unpredictable and potentially life threatening hyperammonemic crises,” Crombez said.
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Five patients in the placebo arm did experience a hyperammonemic crisis, with one patient dying, according to the release. One patient receiving DTX301 had serious acute liver inflammation that was managed with steroids, with liver toxicity representing the most common adverse event in the treatment cohort—a common finding in AAV gene therapies.
Ultragenyx called the safety profile consistent with past trials of DTX301.
Treated patients also self-reported more improvement in symptom severity than patients on placebo did, the California biotech said.
Ultragenyx expects data for the other primary endpoint, which will be assessed in initially treated patients as well as placebo patients that cross over into the treatment arm, in the first half of 2027.
A positive OTC deficiency readout would provide a morale boost for Ultragenyx, as the rare disease specialist has struggled with some setbacks as of late. The company recently resubmitted its application for FDA approval of its Sanfilippo syndrome type A gene therapy, which the agency initially rejected back in July 2025 due to manufacturing concerns.
That gene therapy snub, combined with a pair of phase 3 fails for its brittle bone disease antibody, prompted Ultragenyx to lay off 10% of its workforce last month. Now, the company also has a class-action lawsuit stemming from its communications around the brittle bone disease data to contend with.