Deutetrabenazine effectively treats Huntington’s chorea with minimal side effects

1. In this randomized, controlled trial, Huntington’s patients who received deutetrabenazine had decreased motor abnormalities compared to patient’s treated with placebo.

2. With the exception of diarrhea and somnolence, there were no differences in adverse side-effects between the treatment and placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Treatment of Huntington’s Disease with tetrabenazine can reduce symptomatic chorea. However, as many as 40% of patients have adverse side effects, possibly due to the cytochrome mediated metabolism of the drug. A new, deuterated form of tetrabenazine, deutetrabenazine, may reduce the variability of drug metabolism. To determine if deutetrabenazine is effective for treating Huntington’s chorea, the Huntington Study Group (HSG) performed a multi-site, randomized, controlled trial with patients evenly distributed into treatment and placebo groups for 12 weeks. At the end of the study period, motor function was improved in the treatment compared to placebo group, with significant reductions in chorea and dystonia. No significant deleterious effects were determined for cognition, psychiatric symptoms, or other areas of motor function. While there were a few more cases of diarrhea and somnolence in the treatment group, these symptoms lessened with ongoing treatment, and there were no differences in the rates of other adverse effects between groups.

Though HSG is a non-profit organization, this study was funded by Auspex Pharmaceuticals, and some bias may be inherent in its design and analysis. For instance, while deutetrabenazine showed a significant treatment effect, it’s comparison against placebo is relatively uninformative for clinicians, as it is probable that deutetrabenazine is no more effective than tetrabenazine. Additionally, while the deuterated drug showed few adverse effects, the lack of a direct comparison with tetrabenazine may give prescribers pause, especially since two generic forms of tetrabenazine were FDA approved last year.

Click to read the study, published today in JAMA

Relevant Reading: Deuterated drugs draw heavier backing

In-Depth [randomized controlled trial]: A total of 90 patients (87 completing the study; 96.7%) with a Unified Huntington’s Rating Scale (UHDRS) of 8 or higher without serious psychiatric co-morbidities or recent tetrabenazine treatment were recruited to this multisite, randomized, controlled trial by HSG. Patients were randomized 1:1 to be treated with deutetrabenazine or placebo for 8 weeks of dose optimization therapy and 4 weeks of maintenance therapy. Patients were assessed weekly for a number of primary chorea severity endpoints and secondary motor function endpoints with safety parameters, including psychiatric condition and cognitive function. A one-week washout period and follow-up analysis were also performed.

Patients treated with deutetrabenazine demonstrated improved total maximum chorea scores of -2.5 (95%CI -3.7 to -1.3) with improved performance on self-reported measures of each patient’s impression of their clinical change (PGIC and CGIC scales: p = 0.002). Along with chorea improvement, a small improvement in dystonia symptoms was also observed (-0.8; 95%CI -1.5 to -0.1). No significant differences were noted in psychiatric, cognitive, behavioral, or functional measures, nor were there any differences on numerous laboratory values, vital signs, or EKG tracings. Patients receiving deutetrabenazine did report increased somnolence and diarrhea, but these adverse events mostly disappeared with long treatment durations and no other adverse events were increased in the treatment group. There was, however, an increase in BMI of 0.7 (95%CI 0.3 to 1.2) in the treatment group, though the clinical significance of this is unclear.


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