Ultragenyx announces results from Cohort 2 of DTX301 study

Ultragenyx announced topline “positive” safety and efficacy data from the second dose cohort and positive longer-term data from the first dose cohort of the ongoing Phase 1/2 study of DTX301, an investigational adeno-associated virus, or AAV, gene therapy for the treatment of ornithine transcarbamylase, or OTC deficiency. The 52-week study is designed to enroll patients with late-onset disease who are clinically stable and on a stable dose of alternate pathway medication. All three patients in the second dose cohort received a single dose. As of the September 12, data cutoff date, patient 1 in Cohort 2 had been followed for 24 weeks, patient 2 for 21 weeks, and patient 3 for 18 weeks. The first patient in Cohort 2 demonstrated normalization of ureagenesis to 104% at week 24. The patient had an initial peak effect at Week 6 and then a decline at Week 12 that was associated with initiation of a tapering course of steroids to manage a mild asymptomatic elevation in alanine aminotransferase, or ALT, levels. After discontinuation of steroids, the rate of ureagenesis normalized at Week 20 and remained normal at Week 24, at which time a second course of steroids had been initiated due to mild asymptomatic ALT elevations, which were controlled. The second and third patients in Cohort 2 did not show a clinically meaningful change in rate of ureagenesis at 12 weeks and did not have ALT elevations nor require steroid treatment. The Data Monitoring Committee, or DMC, has completed its review of Week 12 data from Cohort 2 and recommended that Ultragenyx proceed to the third dose cohort of the study. In Cohort 3, three patients will be enrolled and will each receive a single dose. The first patient is expected to be enrolled before the end of 2018, and data from the Cohort 3 are expected in mid-2019.

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