VMAT2 Inhibitor Shown to Improve Tardive Dyskinesia Symptoms

SAN ANTONIO—Deutetrabenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, can improve symptoms of moderate to severe tardive dyskinesia (TD), posters presented at Psych Congress suggest.

One poster outlined results from the double-blind ARM-TD study, which examined response levels of patients taking deutetrabenazine, compared to a placebo group. Symptoms were measured using the Abnormal Involuntary Movement Scale (AIMS), and results were reported on patients with moderate to severe TD, defined by a score of 6 or greater on the scale.

A total of 97 patients were randomized to 1 of the 2 groups for 12 weeks of treatment. The overall score of the treatment group was reduced by 3 points, compared to a 1.6-point drop for the placebo group.

Researchers also grouped participants by the percentage improvement in AIMS score, from a 10% to 90% improvement, in 10% increments. For each level, a higher proportion of deutetrabenazine patients were responders, compared with placebo patients.

Another poster examined the effect of deutetrabenazine on each of the 7 components on the AIMS. The 12-week change in score was analyzed for each component, using a mixed-model for repeated-measures.

Researchers found a reduction in 6 of the 7 component scores was associated with deutetrabenazine.

The largest improvements were seen in the jaw and lips/perioral area. Smaller improvements were seen in the tongue, upper extremities, neck, shoulders, hips (trunk), and lower extremities. Improvement was not observed in facial expression muscles.

Another poster outlined the design of the randomized Phase III AIM-TD trial of deutetrabenazine. A total of 288 patients with moderate to severe TD were assigned to 1 of 3 fixed-dose regimens of the drug (12 mg/day, 24 mg/day or 36 mg/day) or placebo. Patients underwent dose escalation during the first 4 weeks, followed by 8 weeks of maintenance and a 1-week washout period.

Drugmaker Teva Pharmaceutical Industries, which presented the posters, announced results from that trial in September. Each treatment group saw improvements in AIMS scores, compared with placebo, and the change over 12 weeks was significant for the 24-mg/day and 36-mg/day groups, based on the modified intent-to-treat population.

There are currently no FDA-approved treatments for TD. The FDA gave Breakthrough Therapy designation to deutetrabenazine for the treatment of TD in November 2015. Teva expects to file a regulatory submission with the agency before the end of 2016.

– Terri Airov

References

Anderson KE, MD; Factor SA, Jimenez-Shahed J, et al. Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD): A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of Deutetrabenazine for the Treatment of Moderate to Severe Tardive Dyskinesia (TD). Poster presented at 29^th Annual U.S. Psychiatric & Mental Health Congress; October 21-24, 2016; San Antonio, TX. Poster 206.

Fernandez HH, Factor SA, Jimenez-Shahed J, et al. Deutetrabenazine Treatment Effect in Each Component of the Total Abnormal Involuntary Movement Scale (AIMS). Poster presented at the 29^th Annual U.S. Psychiatric & Mental Health Congress; October 21-24, 2016; San Antonio, TX. Poster 207.

Jimenez-Shahed J, Factor SA, Ondo W, et al. Deutetrabenazine is Associated with an Improvement in Involuntary Movements in Patients with Tardive Dyskinesia (TD) as Seen by the High Proportion of Responders to Treatment in the ARM-TD study. Poster presented at the 29^th Annual U.S. Psychiatric & Mental Health Congress; October 21-24, 2016; San Antonio, TX. Poster 208.

Teva Announces Positive Top-Line Data from Second Phase III Study of SD-809 in Tardive Dyskinesia (TD) [press release]. Teva Pharmaceutical Industries: Jerusalem; September 22, 2016.