Evaluating the Effects of Treatment Conversion for Huntington's Chorea

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Tetrabenazine was the first drug approved by the FDA for treatment of chorea associated with HD.
Tetrabenazine was the first drug approved by the FDA for treatment of chorea associated with HD.

A new proof-of-concept study published in JAMA Neurology demonstrated the safety and efficacy of overnight treatment conversion from tetrabenazine to deutetrabenazine in patients with Huntington disease (HD).

Tetrabenazine (Xenazine; Valeant), a VMAT2 inhibitor, was the first drug approved by the Food and Drug Administration (FDA) for treatment of chorea associated with HD, however, it has been associated with tolerability issues due to high peak plasma concentrations and large plasma fluctuation. Deutetrabenazine (Austedo; Teva), another VMAT2 inhibitor, was approved in April 2017. A study (First-HD) evaluating the safety of deutetrabenazine found that it provided significant chorea control and motor improvement along with a favorable safety profile in comparison to placebo; this was attributed to its pharmacokinetic profile.

In the Phase 3, open-label, single-arm ARC-HD study (n=37), researchers aimed to evaluate the safety and efficacy of converting from tetrabenazine to deutetrabenazine in patients with chorea associated with HD in patients stabilized on tetrabenazine. The initial conversion from tetrabenazine to deutetrabenazine was approximately half the daily dose of tetrabenazine. One week after the overnight conversion to deutetrabenazine, the dose was titrated weekly until optimal control. 

Efficacy endpoints were baseline changes in Unified Huntington's Disease Rating Scale (UHDRS) total maximal chorea (TMC) score and total motor score (TMS). Safety endpoints included adverse events, clinical lab tests, vitals, electrocardiograms, and validated scales.

The data showed chorea control was maintained at Week 1 and showed significant improvement by Week 8 (mean change 2.1; <.001). Regarding safety and tolerability, deutetrabenazine was well tolerated with low incidence of neuropsychiatric adverse events. Moreover, subclinical toxicity was not reported with the use of deutetrabenazine. 

Study authors concluded that patients taking tetrabenazine 3 times daily can safely be converted to deutetrabenazine twice daily, while maintaining chorea control. Switching to deutetrabenazine may potentially improve patient compliance with fewer doses, lower total daily doses, and better tolerability.

Reference

Frank S, Stamler D, Kayson E, et al. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of chorea [published online July 10, 2017]. JAMA Neurol. doi:1001/jamaneurol.2017.1352

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