:Study Objective:Tardive dyskinesia (TD), a persistent and potentially disabling movement disorder, is associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine (VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from two long-term phase 3 studies (KINECT 3 [K3], NCT02274558; KINECT 4 [K4], NCT02405091) and a rollover study (1506, NCT02736955), the long-term outcomes of once-daily VBZ on TD were examined in participants who received 40mg or had a dose reduction from 80 to 40mg.Methods:The effects of VBZ 40mg (as well as VBZ 80mg) were evaluated in the following studies: the pivotal K3 study (6 weeks double-blind, placebo controlled), the extension phase of K3 (42 additional weeks of VBZ, 4 week discontinuation), and the open-label K4 study (48 weeks of VBZ, 4 week discontinuation). Completers from K3 extension and K4 were invited to participate in 1506 (up to 72 additional weeks of VBZ or until commercial availability of VBZ). Few participants reached Week 60 (n=4) or Week 72 (n=0) in the 1506 study before termination. Analyses focused on VBZ 40mg in two populations: pooled K3/K4 (participants who received VBZ 40mg throughout K3 or K4 or who had a dose reduction [80/40mg] during K3 or K4); and 1506 (participants who received VBZ 40mg from beginning of K3 or K4 to last visit in 1506 or who had a dose reduction [80/40mg] at any time). Outcomes for the K3/K4 population included mean change from baseline (CFB) in Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48 of K3 or K4. Outcomes for the 1506 population included a Clinical Global Impression of Severity-Tardive Dyskinesia (CGIS-TD) score ≤2 (“normal, not at all ill” or “borderline ill”).Results:In the K3/K4 population, AIMS CFB to Week 48 indicated mean TD improvements in participants who received 40mg continuously (40mg, -5.7 [n=54]) and in those who had a dose reduction to 40mg (80/40mg, -6.2 [n=13]). In addition, a majority of these participants had an AIMS response after 48 weeks of treatment (40mg, 53.7%; 80/40mg, 53.8%). In the 1506 population, the percentage of participants who had a CGIS-TD score ≤2 (rating of “normal, not at all ill” or “borderline ill”) at Week 12 was 63.6% (7/11) in the 40mg group and 30.8% (4/13) in the 80/40mg group. Data from Weeks 24 to 60 of 1506 were limited by the small sample sizes (<10 participants each in 40mg or 80/40mg group at each of these visits).Conclusions:Based on these analyses and results from published studies, VBZ 40mg may be an effective long-term option for some TD patients. Dose reductions from 80 to 40mg, if necessary, did not appear to compromise long-term benefit.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

中文翻译：

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成人迟发性运动障碍 40 毫克/天缬苯那嗪的 123 项长期结果

: 研究目的：迟发性运动障碍 (TD) 是一种持续性且可能致残的运动障碍，与长期接触抗精神病药和其他多巴胺受体阻滞剂有关。Valbenazine (VBZ) 是一种新型、高选择性的囊泡单胺转运蛋白 2 (VMAT2) 抑制剂，被批准用于治疗成人 TD。使用来自两项长期 3 期研究（KINECT 3 [K3]，NCT02274558；KINECT 4 [K4]，NCT02405091）和一项翻转研究（1506，NCT02736955）的数据，每日一次 VBZ 对 TD 的长期结果是在接受 40mg 或剂量从 80mg 减至 40mg 的参与者中进行检查。方法：在以下研究中评估了 VBZ 40mg（以及 VBZ 80mg）的效果：关键的 K3 研究（6 周双盲，安慰剂对照)，K3 的扩展阶段（VBZ 额外 42 周，4 周停药）和开放标签 K4 研究（48 周 VBZ，4 周停药）。来自 K3 扩展和 K4 的完成者被邀请参加 1506（最多 72 周的 VBZ 或直到 VBZ 的商业可用性）。在终止前的 1506 研究中，很少有参与者达到第 60 周（n=4）或第 72 周（n=0）。分析集中在两个人群中的 VBZ 40mg：合并 K3/K4（在 K3 或 K4 期间接受 VBZ 40mg 或在 K3 或 K4 期间减少剂量 [80/40mg] 的参与者）；和 1506（从 K3 或 K4 开始到 1506 年最后一次访问接受 VBZ 40mg 或在任何时间减少剂量 [80/40mg] 的参与者）。K3/K4 人群的结果包括在第 48 周的异常不自主运动量表 (AIMS) 总分（项目 1-7 的总和）和 AIMS 反应（从基线的总分提高≥50%）的平均变化（CFB） K3 或 K4。1506 名人群的结果包括严重迟发性运动障碍的临床总体印象 (CGIS-TD) 评分≤2（“正常，完全没有生病”或“处于临界状态”）。结果：在 K3/K4 人群中，AIMS CFB至第 48 周，表明连续接受 40mg 的参与者（40mg，-5.7 [n=54]）和剂量减少至 40mg 的参与者（80/40mg，-6.2 [n=13]）的平均 TD 改善。此外，这些参与者中的大多数在治疗 48 周后出现 AIMS 反应（40mg，53.7%；80/40mg，53.8%）。在 1506 名人群中，CGIS-TD 评分≤2（“正常，在第 12 周，40mg 组和 80/40mg 组分别为 63.6% (7/11) 和 30.8% (4/13)。1506 周的第 24 至 60 周的数据受到小样本量的限制（每次访问时 40mg 或 80/40mg 组中的每人 <10 名参与者）。结论：基于这些分析和已发表研究的结果，VBZ 40mg 可能是对一些 TD 患者来说是一种有效的长期选择。如有必要，将剂量从 80 毫克减少到 40 毫克，似乎并没有损害长期利益。资金致谢：本研究由 Neurocrine Biosciences, Inc. 赞助。结论：基于这些分析和已发表研究的结果，VBZ 40mg 可能是一些 TD 患者的有效长期选择。如有必要，将剂量从 80 毫克减少到 40 毫克似乎并没有损害长期利益。 资金致谢：本研究由 Neurocrine Biosciences, Inc. 赞助。结论：基于这些分析和已发表研究的结果，VBZ 40mg 可能是一些 TD 患者的有效长期选择。如有必要，将剂量从 80 毫克减少到 40 毫克，似乎并没有损害长期利益。资金致谢：本研究由 Neurocrine Biosciences, Inc. 赞助。