Deutetrabenazine for tardive dyskinesia and chorea associated with Huntington’s disease: a review of clinical trial data

ABSTRACT

Introduction: Huntington’s disease (HD)-associated chorea and tardive dyskinesia (TD) are hyperkinetic movement disorders that can have deleterious effects on patients’ quality of life (QoL). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of HD-associated chorea and TD. It is structurally similar to tetrabenazine, an FDA-approved compound for treatment of chorea that is widely used off-label for treatment of TD, but has deuterium modifications that improve its pharmacokinetic profile.

Areas covered: Herein, the authors cover the key clinical trials with deutetrabenazine in patients with HD-associated chorea (First-HD and ARC-HD) and in patients with TD (ARM-TD, AIM-TD, and RIM-TD).

Expert opinion: Deutetrabenazine demonstrates consistent efficacy across patient types regardless of underlying psychiatric illness, or through use of dopamine-receptor antagonists (DRAs), which are the primary cause of TD. The safety profile of deutetrabenazine in clinical trials is similar to that of placebo. Long-term extension studies in both HD-associated chorea and TD show consistent efficacy and safety. Deutetrabenazine will likely be an integral part of the treatment strategy for HD-associated chorea and TD. Meanwhile, its potential to treat other hyperkinetic movement disorders is still under investigation.

KEYWORDS:

• Antipsychotics
• deutetrabenazine
• Huntington’s disease
• movement disorders
• tardive dyskinesia
• tetrabenazine
• valbenazine
• VMAT2 inhibitor

Box 1. Drug summary box.

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Article highlights

• Deutetrabenazine is a vesicular monoamine transport type 2 (VMAT2) inhibitor approved by the United States Food and Drug Administration in 2017 for the treatment of Huntington’s disease (HD) and tardive dyskinesia (TD)

• The pharmacokinetic profile of deutetrabenazine allows for less-frequent administration at a lower dosage while maintaining similar systemic exposure.

• We review efficacy and safety in Phase 3 and long-term extension studies, for both TD and HD-associated chorea, emphasizing long-term safety and tolerability.

• In patients with psychiatric comorbidities, we do not see any safety and efficacy impediments to concomitant deutetrabenazine and dopamine receptor antagonist use

Acknowledgments

M Howell, D Meyen and M Coakley of Chameleon Communications International are gratefully acknowledged for their editorial/writing assistance in preparing this article.

Declaration of interest

M Philbin is a Director at and B Carroll an employee of Teva Pharmaceuticals, Meanwhile, D Claassen has received grant support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Michael J Fox Foundation, the Huntington’s Disease Society of America, Vaccinex, AbbVie, Auspex Pharmaceuticals. He has also received consulting fees from Teva Neuroscience, Lundbeck, Acadia, and AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One referee declares that they have consulted for Teva and Auspex in work related to deutetrabenazine development while another referee was involved in studies on tetrabenazine and deutetrabenazine in the past but has no financial incentive. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was funded by Teva Pharmaceuticals. Writing assistance by Chameleon Communications International was utilized in the preparation of this manuscript and was funded by Teva Pharmaceuticals.