Positive Topline Results Released from Study of Gene Therapy in OTC Deficiency


Ultragenyx Pharmaceutical, Inc. released positive long-term safety and efficacy data from the first dose cohort of the Phase 1/2 study of DTX301. The investigational AAV gene therapy, is intended for the treatment of OTC deficiency.

This morning, Ultragenyx Pharmaceutical, Inc. released positive long-term safety and efficacy data from the first dose cohort of the Phase 1/2 study of DTX301.

The drug, an investigational adeno-associated virus (AAV) gene therapy, is intended for the treatment of ornithine transcarbamylase (OTC) deficiency.

The 52-week study enrolled patients with late-onset disease who are clinically stable and on a stable dose of alternate pathway medication. In the first, lowest-dose cohort, three patients received a single DTX301 dose of 2.0 × 10^12 GC/kg.

To evaluate therapeutic response of DTX301, the study measured the change in the rate of ureagenesis, or the process of converting the potent neurotoxin ammonia into urea for excretion. Patients with OTC are deficient in this pathway.

The pre-defined endpoint for efficacy evaluation occurred 12 weeks after dosing. The first patient’s rate of ureagenesis was normalized, maintained and then substantially increased over 24 weeks. In the 3 weeks since the stoppage of medication, the patient has been reported by the investigator to be doing well clinically. The second and third patients did not show a clinically meaningful change in rate of ureagenesis over 20 and 12 weeks, respectively.

The Data Monitoring Committee (DMC) has completed its review of the current Cohort 1 data, and Ultragenyx will process to the second, higher-dose cohort of the study. Three patients will be enrolled in Cohort 2, and the first is expected to be enrolled this month. Data from the second cohort are expected in the second half of 2018.

“Longer term data from the first, lowest-dose cohort show that patient 1 maintained and substantially increased levels of ureagenesis through 24 weeks and we view these results as a promising indication of the potential and durability of DTX301. Based on these positive results at 24 weeks, this patient opted to discontinue all alternate pathway medication three weeks ago per the trial protocol and continues to do well,” said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx in a press release.

As of February 15, 2018, there were no infusion-related adverse events (AEs) and no serious AEs reported. All AEs have been Grade 1 or Grade 2 and all have been resolved.

“The data monitoring committee has completed a favorable review of the current data for this dosing cohort,” continued Dr Kakkis. “We were encouraged by the initial signs of efficacy with an acceptable safety profile in the first cohort, which is at the low end of the expected dosing range. We are pleased to advance this study to the second, higher-dose cohort.”

According to the National Institute of Health (NIH), more than approximately 10,000 patients are affected by OTC deficiency worldwide, of which an estimated 80% are classified as late-onset and represent a clinical spectrum of disease severity.

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