Tardive Dyskinesia Drug Safe, Effective for Huntington's Chorea

A drug currently approved for tardive dyskinesia (TD) is also effective at treating Huntington's disease (HD)–associated chorea, a movement disorder that affects most patients with HD, new phase 3 trial results show.

Valbenazine is in the same class as two other drugs already approved for HD-related chorea. However, researchers suggest the TD drug may have benefits over those medications, including its once-daily dosage and safety profile.

In the KINECT-HD trial, which included almost 130 patients, those who received valbenazine showed significantly greater chorea symptom-improvement scores than those who received matching placebo. In addition, there was no increase in suicidal ideation or behavior.

"We know that not all chorea is symptomatic, but when chorea is problematic, it should be addressed," lead investigator Erin Furr-Stimming, MD, neurologist and director of the Huntington's Disease Society of America Center of Excellence with McGovern Medical School at UTHealth, Houston, Texas, told Medscape Medical News.

"Based on our work and others', we feel that there is an unmet medical need for the symptomatic treatment of chorea in HD," Furr-Stimming said.

The findings were presented at the American Academy of Neurology (AAN) 2022 Annual Meeting.

No Black-Box Warning?

HD affects more than 35,000 individuals in the United States. About 90% of these patients experience chorea, which includes involuntary, nonrhythmic movements that appear to flow from one muscle to another.

Tetrabenazine and deutetrabenazine, both vesicular monoamine transporter 2 (VMAT2) inhibitors, are approved by the US Food and Drug Administration (FDA) for the treatment of HD-related chorea. Both drugs require multiple daily doses.

Valbenazine, which was approved in 2017 for use in patients with TD, is also a VMAT2 inhibitor ― but is only taken once a day.

To measure the drug's effectiveness in treating HD-associated chorea, researchers enrolled 128 patients with HD, aged 18 to 75 years and with untreated chorea, in a phase 3, randomized, double-blind, placebo-controlled trial.

Participants received either a starting valbenazine dose of 40 mg daily that was titrated up to a maximum of 80 mg during the 12-week study or matching placebo.

Results showed that patients who received valbenazine reported significantly better improvement in chorea severity compared with the placebo group, as measured by the Total Maximal Chorea score (mean change from baseline, -4.6 vs -1.4; P < .0001).

There were no significant between-group differences in neuro quality of life (QoL) or in upper and lower extremity physical function.

The most common adverse event was sleepiness, which was reported by 15.6% of the valbenazine group and 3.2% of the placebo group. No suicidal behavior or worsening of suicidal ideation was observed in the valbenazine group.

That is important because both of the approved drugs for HD-associated chorea carry black-box warnings for depression and suicidality in patients with HD, the investigators note. Valbenazine for TD does not have that warning and has been on the market for 5 years.

Daily-Dosing Benefit

Commenting on the findings for Medscape Medical News, neurologist Joseph Jankovic, MD, distinguished chair in movement disorders and director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, Houston, Texas, said the once-daily dosing of valbenazine could be important for some patients with HD.

"While tetrabenazine and deutetrabenazine have been found to be effective in the treatment of chorea associated with HD, both of these drugs have some limitations, including the need for multiple daily dosing," said Jankovic, who was not involved with the research.

"Valbenazine has the advantage of once-a-day administration, which may improve compliance, particularly in patients with HD who may have cognitive impairment," he added.

One disappointing finding in the study, however, was the lack of improvement in neuro QoL.

"But this is not surprising, as in our discussions with FDA before the approval of tetrabenazine, we had to make a case that improvement in chorea does translate into improvement in QoL in patients with HD," Jankovic said.

The study was funded by Neurocrine Biosciences. Furr-Stimming has received funding from the Huntington Study Group provided by Neurocrine Biosciences. Jankovic reported no relevant financial relationships.

American Academy of Neurology (AAN) 2021 Annual Meeting: Abstract 1199. Presented April 5, 2022.

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