Treatment Responses with Long-Term Valbenazine in Patients with Tardive Dyskinesia (1663)

Objective: To evaluate the range of responses in adults with tardive dyskinesia (TD) who received once-daily valbenazine for 48 weeks. Background: Valbenazine, a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the treatment of TD in adults. Valbenazine clinical trials used a more rigorous definition of response than previous TD trials, including ≥50% improvement in Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) and score ≤2 (“much improved” or better) on the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) or Patient Global Impression of Change (PGIC). Because participants who did not meet these thresholds still potentially experienced meaningful improvements, data from KINECT 4 (NCT02405091) were analyzed post hoc using wider ranges of response. Design/Methods: KINECT 4 included adults (18–85 years) with stable schizophrenia/schizoaffective disorder or mood disorder, TD for ≥3 months, and no/minimal risk of suicidality. Valbenazine was initiated at 40 mg and increased to 80 mg at Wk4 if tolerated; dosage was reduced to 40 mg after Wk4 if not tolerated. Response ranges at Wk48 were as follows: AIMS, ≥10% to 100% improvement; CGI-TD and PGIC, score ≤3 (“minimally improved” or better) or ≤2 (“much improved” or better). Results: Among participants with an available assessment at Wk48 (N=103), 94.2% had ≥30% improvement and 86.4% had ≥50% improvement in AIMS total score. Response rates for remaining AIMS thresholds ranged from 9.7% (100% response) to 97.1% (≥10% response). Almost all participants had a global score ≤3: CGI-TD, 99.0%; PGIC, 98.1%. Most had a global score ≤2: CGI-TD, 92.2%; PGIC, 88.3%. Conclusions: After 48 weeks of once-daily valbenazine treatment, 97% of the participants had some AIMS response (≥10% improvement) with 9.7% reaching 100% AIMS response. Most participants (>98%) had a global rating of “minimally improved” or better, and >88% had a global rating of “much improved” or better. Disclosure: Dr. Singer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with I have received payment for my work as a video panelist from CNS Ratings LLC reviewing videos for a Mitsubishi Pharmaceutical sponsored study.. Dr. Singer has received research support from Sunovion, Adamas, Pharma2B, Biogen. Dr. Comella has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda Therapeutics, Allergan, Lundbeck Ltd., Merz Pharmaceuticals, Acadia Pharmaceuticals, Ipsen Pharmaceuticals, Jazz Pharmaceuticals, Neurocrine Biosciences Inc., Revance Therapeutic, Sunovion, and AEON Biopharma. Dr. Comella has received research support from Acorda, Revance, Merz, Eisai, and Jazz Pharmaceutical.Dr. Marder has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting for Sunovion, Roche.. Dr. Marder has received personal compensation in an editorial capacity for Uptodate for editor; Oxford U Press for editor. Dr. Marder has received research support from Takeda and Boeringer-Ingelheim provided research support. Dr. Farahmand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Neurocrine Biosciences, Inc. Dr. Jimenez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine Biosciences Inc.