Ultragenyx has Released Updates on Their Study of a Potential Gene Therapy for OTC Deficiency

Ultragenyx Pharmaceuticals has shared data from two cohorts taking part in an on-going study involving an investigational gene therapy for ornithine transcarbamylase deficiency. For more information, you can view the source press release at Ultragenyx’s website by clicking here.

About Ornithine Transcarbamylase (OTC) Deficiency

OTC deficiency is a genetic disorder that causes patients to lack the OTC enzyme. This enzyme is one of six enzymes that are involved in the urea cycle, which removes nitrogen from the body. Without enough of the OTC enzyme, people who have OTC deficiency develop a build-up of nitrogen in the form of ammonia, which leads to symptoms of OTC deficiency. These vary in their form and severity between patients. 

About the Gene Therapy

Ultragenyx is investigating a potential gene therapy for OTC deficiency, called DTX301. It is an AAV type 8 gene therapy that has been found to normalise urinary orotic acid levels (a sign of ammonia metabolism) in preclinical studies. Both the US and Europe have granted DTX301 Orphan Drug Designation.

The On-Going Phase 1/2 Study

DTX301 is being further researched in an on-going Phase 1/2 clinical trial that is measuring changes to the rate of ureagenesis in patients. Ureagenesis is the conversion of ammonia into urea for removal, and is a process that is affected by OTC deficiency. The researchers plan to test the gene therapy in three groups of patients (cohorts) in this study, with each group receiving a different dosage level. However, treatment of the cohorts has been staged, so that progression to the next dosage level group depends on the last one showing acceptable safety. Ultragenyx has recently released data from the first two cohorts.

The First Cohort

According to the press release, the first patient with normalised ureagenesis in Cohort 1 has finished the 52-week study, and, at which point they still had a higher level of ureagenesis and clinical stability, even after they ended alternate pathway medication and changed their protein-restricted diet.

The Second Cohort

One patient in the second cohort has achieved a normalised level of ureagenesis, although the second and third patients in this group haven’t shown changes to their rates of ureagenesis. However, as of the data cutoff point (12th September 2018), no serious adverse events or infusion-related adverse events have been reported for this group. Based on this, there are plans to go ahead with the third cohort, and enrolment is expected to begin this year, with data becoming available in mid-2019.


Anna Hewitt

Anna Hewitt

Anna is from England and recently finished her undergraduate degree. She has an interest in medicine and enjoys writing. In her spare time she likes to cook, hike, and hang out with cats.

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