FDA Clears Deutetrabenazine (Austedo) for Huntington's Chorea

Megan Brooks

Disclosures

April 04, 2017

The US Food and Drug Administration (FDA) has approved deutetrabenazine (Austedo, Teva Pharm Ltd) for the treatment of chorea associated with Huntington's disease (HD), the company has announced.

Deutetrabenazine, which had orphan drug status, is a deuterated form of the vesicular monoamine transporter 2 inhibitor tetrabenazine (Xenazine, Lundbeck Inc). It's the first deuterated product approved by the FDA and only the second product approved for HD, the company said.

HD affects more than 35,000 people in the United States. Chorea, in which patients experience involuntary, random, and sudden twisting and/or writhing movements, occurs in about 90% of patients with HD at some point in the course of their illness.

"Chorea associated with Huntington's disease has a significant impact on those living with the disease and their families," Louise Vetter, chief executive officer of the Huntington's Disease Society of America, said in a Teva news release.   

The approval of deutetrabenazine "represents an important new treatment option for people with HD and highlights the need for more therapeutic resources for this underserved patient community," Vetter added.

The efficacy of deutetrabenazine for HD-associated chorea was demonstrated in a double-blind multicenter trial conducted in 90 ambulatory patients at 34 centers in the United States and Canada, with 45 patients randomly assigned to deutetrabenazine and 45 to placebo.  Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout.

The patients had a baseline total maximal chorea score of 8 or higher. In the trial, the Unified Huntington's Disease Rating Scale total maximal chorea scores for patients taking deutetrabenazine improved by about 4.4 units from baseline to the maintenance period (average of week 9 and week 12), compared with approximately 1.9 units for patients taking placebo. 

The treatment effect of –2.5 units was statistically significant (P < .0001).

Deutetrabenazine was also associated with improvements in the 36-Item Short Form Health Survey physical functioning subscale score, the Patient Global Impression of Change, and the Clinical Global Impression of Change scales, but not the Berg Balance Test.

The results of the trial were published in JAMA in 2016 and reported by Medscape Medical News at that time.    

The most common adverse reactions (>8% of deutetrabenazine-treated patients; greater than seen in placebo group) were somnolence, diarrhea, dry mouth, and fatigue.

Deutetrabenazine contains a boxed warning about an increase in the risk for depression and suicidal thoughts and behavior (suicidality) in patients with HD. Patients, caregivers, and families should be informed of the risk for depression and suicidality and instructed to report behaviors of concern promptly to their healthcare provider, the label advises.

The drug is contraindicated in patients who are suicidal and in patients with untreated or inadequately treated depression.

Deutetrabenazine is also contraindicated in patients with hepatic impairment; patients taking monoamine oxidase inhibitors (MAOIs) or those within 14 days of discontinuing MAOI therapy; patients taking reserpine or within 20 days of discontinuing reserpine; and patients taking tetrabenazine.

Deutetrabenazine may increase the risk for akathisia, agitation, and restlessness and may cause parkinsonism in patients with HD. Sedation is a common dose-limiting adverse reaction.

Clinically relevant QT prolongation may occur in some patients treated with deutetrabenazine who are poor metabolizers of CYP2D6 or are coadministered a strong CYP2D6 inhibitor.

Complete prescribing information for deutetrabenazine is available here.  
Teva's Shared Solutions provides support to patients starting or taking deutetrabenazine. The telephone number is 1-800-887-8100. Deutetrabenazine is expected to be available in the United States within the next 3 weeks, the company said.

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