EFFECTS OF LONG-TERM VALBENAZINE IN KINECT 4: POST HOC RESPONSE AND SHIFT ANALYSES IN YOUNGER AND OLDER ADULTS WITH TARDIVE DYSKINESIA

Introduction Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged antipsychotic exposure. Compared to younger patients, older patients have a higher risk of TD and may develop symptoms earlier during antipsychotic treatment. Valbenazine, a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved to treat TD in adults of all ages, with no dose adjustment required for older patients. The long-term effects of valbenazine on TD were evaluated in KINECT 4 (NCT02405091), an open-label study in which participants received up to 48 weeks of once-daily treatment with valbenazine. Abnormal Involuntary Movement Scale (AIMS) data from this study were analyzed post hoc to evaluate treatment responses in older (≥55 to 85 years) and younger (18 to <55 years) patients. Methods KINECT 4 included participants who met the following criteria: ages 18 to 85 years; DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or mood disorder; neuroleptic-induced TD for ≥3 months prior to screening; stable psychiatric status (Brief Psychiatric Rating Scale score <50); no high risk of active suicidal ideation or behavior. Stable doses of concomitant medications to treat psychiatric and medical disorders were allowed. Valbenazine dosing was initiated at 40?mg, with escalation to 80?mg at Week 4 based on clinical assessment of TD and tolerability; a dose reduction to 40?mg was allowed per clinical need. AIMS responses, ranging from ≥10% to 100% improvement from baseline in AIMS total score (sum of items 1-7), were analyzed at Week 48 based on scoring by site investigators, with certain thresholds defined descriptively as follows: minimal response (≥10% total score improvement from baseline); clinically meaningful response (≥30% improvement); robust response (≥50% improvement [protocol-defined threshold for AIMS response]); and maximal response (80-100% improvement). To further evaluate clinically meaningful changes in TD symptoms, shift analyses were conducted for each AIMS item (representing 7 different body regions) as follows: improvement/shift from score ≥3 (moderate/severe) at baseline to score ≤2 (none/minimal/mild) at Week 48. Results Of 163 participants in the safety/efficacy population, 103 (63.2%) had an available AIMS assessment at Week 48. At Week 48, the percentages of patients who met the criteria for minimal response (≥10% AIMS total score improvement from baseline) or clinically meaningful (≥30% improvement) response were similar between the older and younger subgroups (≥55 years; <55 years): minimal (97.1% [68/70]; 97.0% [32/33]); clinically meaningful (95.7% [67/70]; 90.9% [30/33]). For higher thresholds of AIMS response, older patients seemed more likely to experience improvements, as indicated by results for robust response (88.6% [62/70]; 81.8% [27/33]) and maximal response (44.3% [31/70]; 27.3% [9/33], which included 10 total patients who had 100% improvement (11.4% [8/70]; 6.1% [2/33]). For shift analyses (defined as AIMS item score ≥3 at baseline and score ≤2 at Week 48), some results were limited by small sample sizes. However, 100% of both older and younger participants met the shift criteria for lips, upper extremities, and lower extremities. Results for the remaining AIMS items were as follows (≥55?years, <55 years): face (100% [29/29], 91.7% [11/12]); jaw (97.4% [37/38], 100% [13/13]); tongue (100% [44/44], 93.3% [14/15]);and trunk (100% [18/18], 62.5% [5/8]). Conclusions After 48 weeks of treatment with once-daily valbenazine, >95% of all KINECT 4 participants (older and younger) had a minimal AIMS total score response (≥10% improvement), >90% had a clinically meaningful response (≥30% improvement), and >80% had a robust response (≥50% improvement). Older patients seemed more likely than younger patients to achieve a maximal response, including 100% improvement, although these results may be limited by smaller sample sizes. Shift analyses based on AIMS item scores were supportive of AIMS total score responses. Together, the results presented in this post hoc analysis suggest that valbenazine is an appropriate long-term treatment for both older and younger adults with TD. This research was funded by: This study was sponsored by Neurocrine Biosciences, Inc.