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BackgroundIndividuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.MethodsParticipants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs).ResultsAt study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4).ConclusionsValbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.

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 (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.

Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

ObjectiveVesicular monoamine transporter 2 (VMAT2) inhibitors including valbenazine are first-line therapies for tardive dyskinesia (TD), a persistent movement disorder associated with antipsychotic exposure. This real-world study was performed to assess the association between patient awareness of TD symptoms and clinician-assessed symptom severity.MethodsClinicians who treated antipsychotic-induced TD with a VMAT2 inhibitor within the past 24 months were asked to extract demographic/clinical data from patients charts and complete a survey for additional data, including patient awareness of TD (yes/no) and TD symptom severity (mild/moderate/severe).ResultsData for 601 patients were provided by 163 clinicians (113 psychiatrists; 46 neurologists; 4 primary care physicians). Patient demographics: 50% male; mean age 50.6 years; 55% schizophrenia/schizoaffective disorder; 29% bipolar disorder; 16% other psychiatric diagnoses. Positive relationships were seen between patient awareness and clinician-assessed symptom severity. Awareness was highest in patients with severe symptoms in specific body regions: face (88% vs 78%/69% [awareness by severe vs moderate/mild symptoms]); jaw (90% vs 80%/67%); wrists (90% vs 69%/63%). In other regions, awareness was similar in patients with severe or moderate symptoms: lips (85%/86% vs 68% [severe/moderate vs mild]); tongue (81%/80% vs 73%); neck (80%/78% vs 68%); arms (67%/66% vs 62%); knees (67%/67% vs 53%).ConclusionsIn patients prescribed a VMAT2 inhibitor for TD, patient awareness was generally higher in those determined to have moderate-to-severe symptom severity as assessed by the clinician. More research is needed to understand how awareness and severity contribute to TD burden, and whether different treatment strategies are needed based on these factors.FundingNeurocrine Biosciences, Inc.

ObjectiveThe Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) is usually the primary efficacy measure in tardive dyskinesia (TD) clinical trials. However, item 8 of the AIMS (clinician’s global impression of severity) might also be an appropriate assessment in real-life healthcare settings. To explore the potential of item 8 as a clinical measure, post hoc analyses were conducted using data from a long-term study of valbenazine, an approved TD medication.MethodsIn KINECT 4 (NCT02405091), adults with TD received once-daily valbenazine (40 or 80 mg) for 48 weeks. Analyses included two sets of AIMS item 8 scores: based on investigators ratings of item 8 using protocol-defined descriptors; and based on investigators highest scores from items 1–7 (analyzed post hoc). Shift analyses included an improvement from score =3 at baseline (moderate or severe) to score =2 at Week 48 (none to mild).ResultsAt baseline in all participants (N=163), AIMS item 8 mean scores were 3.2 (protocol) and 3.3 (post hoc). In participants with a score =3 at baseline per investigators ratings using protocol-defined descriptors, 95.9% [94/98] shifted to a score =2 by Week 48. A similar result (93.9% [93/99]) was found when item 8 was based on investigators highest scores from items 1–7.ConclusionShift analyses using AIMS item 8 scores indicated that most participants in KINECT 4 had a clinically meaningful improvement after 48 weeks of once-daily treatment with valbenazine. AIMS item 8 may be an appropriate clinical measure for assessing changes in TD severity.FundingNeurocrine Biosciences, Inc.

IntroductionTardive Dyskinesia (TD) refers to abnormal, involuntary, choreoathetoid movements of the tongue, lips, face, trunk, and extremities and is associated with long-term exposure to dopamine-blocking agents, such as antipsychotic medications. Once established, these movements usually persist. The movements are disfiguring and can bring unwanted attention to affected individuals. When severe, especially if the respiratory muscles are affected, the movements can be disabling, limit activity, and reduce quality of life. The prevalence is 7.2% in individuals on newer antipsychotics who have never been exposed to older neuroleptics. Until recently, there were no effective treatments for TD. In recent years, many new treatments have been investigated for the treatment of TD, including valbenazine, deutetrabenazine, and branched chain amino acids. Valbenazine first, followed by deutetrabenazine are FDA approved to treat TD. A virtual broadcast was developed to assess the ability of continuing medical education (CME) to improve awareness of the recognition and treatment of TD among psychiatrists.MethodsThe virtual broadcast (May 9, 2020) consisted of a two-hour, live-streamed discussion between two expert faculty. Impact of the educational activity was assessed by comparing psychiatrists’ responses to four identical questions presented before and directly after activity participation. A follow-up survey was sent to all participants six-weeks post-activity to measure performance in practice changes. A chi-square test was used to identify significant differences between pre- and post-assessment responses. Cohen’s d was used to calculate the effect size of the virtual broadcast.ResultsActivity participation resulted in a noticeable educational effect among psychiatrists (n=621; d=6.12, PConclusionsThe results indicated that a CME-certified two-hour virtual broadcast was effective at improving knowledge among psychiatrists for the recognition and treatment of TD. This knowledge also resulted in positive changes in practice performance post-activity. Future education should continue to address best practices in the diagnosis, treatment and management of patients with TD, as there remains an increased need for tailored CME among psychiatrists.FundingNeurocrine Biosciences, Inc.

Study Objective:Valbenazine (VBZ) is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged antipsychotic exposure. Post hoc response and shift analyses were conducted using Abnormal Involuntary Movement Scale (AIMS) data from KINECT 4 (NCT02405091), a long-term open-label study in which participants received up to 48 weeks of open-label treatment with once-daily VBZ (40 or 80 mg).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 Results:103 participants had an available AIMS assessment at Week 48 (40 mg, n=20; 80 mg, n=83 [including 9 with a dose reduction]). At Week 48, 94.2% of participants had ≥30% total AIMS score improvement (40 mg, 90.0%; 80 mg, 95.2%) and 86.4% had ≥50% improvement (40 mg, 90.0%; 80 mg, 85.5%). The percentage of participants meeting the remaining AIMS response thresholds ranged from 9.7% (for 100% response) to 97.1% (for ≥10% response). In participants who had an AIMS item score ≥3 at baseline, shifts to a score ≤2 at Week 48 were as follows: 100% for lips, upper extremities, and lower extremities (VBZ 40 mg and 80 mg). Shift rates for the remaining regions were as follows (40 mg, 80 mg): face (100% [9/9], 96.9% [31/32]), jaw (100% [10/10], 97.6% [40/41]), tongue (100% [11/11], 97.9% [47/48]), trunk (87.5% [7/8], 88.9% [16/18]).Conclusions:After 48 weeks of treatment with once-daily VBZ (40 or 80 mg), >85% of KINECT 4 participants had a clinically meaningful AIMS response (≥30% total score improvement), a robust AIMS response (≥50% total score improvement), or an AIMS shift (from item score ≥3 at baseline to score ≤2 at Week 48). These results suggest that VBZ is an appropriate long-term treatment for many adults with TD.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

BackgroundPatients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.MethodsKINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score ResultsOf 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.ConclusionSustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.

ObjectiveValbenazine (VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat tardive dyskinesia (TD) in adults. It has been evaluated in 2 long-term studies (KINECT 3, KINECT 4) in which participants received VBZ (40 or 80mg) for up to 48weeks. This long-term rollover study (NCT02736955) was conducted to evaluate global TD improvement and patient satisfaction with once-daily VBZ.MethodsKey eligibility criteria: age 18 to 85 years; completion of KINECT 3 or KINECT 4; maintenance medications (for schizophrenia, schizoaffective disorder, or mood disorder) at stable doses; Brief Psychiatric Rating Scale score Results160 participants with available data were included in analyses (40mg =35; 80mg =117; 80/40mg =8); 138 were receiving treatment when VBZ became commercially available. The percentages of participants who completed visits at Wks 12, 24, 36, and 48 were 96.3%, 78.1%, 56.9% and 35.0%, respectively. Few reached Wk 60 (n=4) or Wk 72 (n=0) due to commercial availability. The percentage of participants with CGIS-TD score ≤2 (“normal, not at all ill” or “borderline ill”) increased from baseline (before restarting VBZ) (40mg, 5.7%; 80mg, 18.1%) to Wk 48 (40mg , 41.7%; 80mg , 74.4%). At baseline, almost all participants rated their prior VBZ experience with a PSQ score ≤2 (“very satisfied” or “somewhat satisfied”) (40mg , 100%, 80mg , 99.1%). Similar results were seen at the Wk 48 visit, with most participants continuing to express satisfaction with VBZ (40mg , 100%; 80mg , 97.4%).ConclusionsA clinician-based global assessment indicated ongoing, meaningful TD improvements in adults who received once-daily VBZ in the current study. In participants treated for >1 year, continued patient satisfaction rates with VBZ were high.Funding Acknowledgements: Neurocrine Biosciences, Inc.

ObjectiveValbenazine is approved for tardive dyskinesia (TD) in adults based on clinical trials that included patients with mood disorders (e.g., bipolar disorder, major depressive disorder). In two long-termphase 3 trials, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091), sustained TD improvements were found in participants who received once-daily treatment with valbenazine (40 or 80mg). Data from these studies were analyzed post hoc to evaluate changes in psychiatric status of patients with a primary mood disorder.MethodsData were pooled from participants with mood disorders in KINECT 3 (6-week double-blind, placebo-controlled period; 42-week double-blind extension period; 4-week drug-free washout) and KINECT 4 (48week open-label treatment; 4-week drug-free washout). At screening, patients must have had a Brief Psychiatric Rating Scale total score ResultsOf the 95 participants with a primary mood disorder (40mg , n=32; 80mg , n=63), 59 (62.1%) were diagnosed with bipolar disorder, 32 (33.7%) with major depressive disorder, and 4 (4.2%) with another mood disorder. A majority of all mood participants received concomitant antidepressants (84.2%) and/or antipsychotics (76.8%) during treatment; other common concomitant medications included antiepileptics (47.4%), anxiolytics (38.9%), and anticholinergics (22.1%). Mean YMRS and MADRS total scores in all mood participants indicated mood symptom stability at baseline (YMRS, 2.7; MADRS, 5.9). This stability was maintained during the studies, as indicated by minimal changes from baseline in mean total scores (YMRS: Week 48, 1.0; Week 52, –1.0; MADRS: Week 48, 0.3; Week52,0.9). Changes in individual items on both scales were also small (ConclusionsMood symptom stability was maintained in patients with TD and a primary mood disorder who received up to 48 weeks of treatment with once-daily valbenazine in addition to their psychiatric medication(s).Funding Acknowledgements: Neurocrine Biosciences, Inc.

Study ObjectivesValbenazine (INGREZZA; VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is approved for the treatment of tardive dyskinesia (TD) in adults. The randomized, double-blind, placebo (PBO)-controlled trials of VBZ evaluated the treatment of TD in patients with a primary psychiatric diagnosis (schizophrenia/schizoaffective disorder or mood disorder) while on concomitant psychiatric medications to manage these disorders. Since treatment-emergent depression and suicidal ideation/behavior are important clinical concerns in psychiatric patient populations, data from these trials were analyzed to assess the effectsof once-daily VBZ on depression and suicidality.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Outcome data were analyzed in the safety population by pooled VBZ doses (40 mg, 80 mg) and PBO. Outcomes of interest included: treatment-emergent adverse events (TEAEs) related to depression or suicidality; mean score change from baseline to Week 6 in the Calgary Depression Scale for Schizophrenia (CDSS, for participants with schizophrenia/schizoaffective disorder) or the Montgomery-Åsberg Depression Rating Scale (MADRS, for participants with mood disorder); and, worsening from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation scores. All outcomes were analyzed descriptively.ResultsThere were 400 total participants in the pooled safety population; 286 participants had schizophrenia/schizoaffective disorder (40 mg, n=82; 80 mg, n=70; PBO, n=134) and 114 had a mood disorder (40 mg, n=28; 80 mg, n=42; PBO, n=44). Over one-third of participants had a lifetime history of suicidal ideation or behavior (40 mg, 45%; 80 mg, 39%; PBO, 37%). Few participants had a depression- or suicide-related TEAE, with no apparent differences between VBZ and PBO: suicidal ideation (40 mg, 3.6%; 80 mg, 0.9%; PBO, 2.2%); depression (40 mg, 0%; 80 mg, 1.8%; PBO, 1.1%); depressive symptom (40 mg, 0.9%; 80 mg, 0%; PBO, 0.6%); suicide attempt (40 mg, 0%; 80 mg, 0.9%; PBO, 0%). Mean changes from baseline to Week 6 in depression scale scores were generally small and similar across treatment groups: CDSS total score (40 mg, -0.5; 80 mg, -0.6; PBO, -0.3); MADRS total score (40 mg, -0.2; 80 mg, -1.7; PBO, 0.6). Few participants had a shift from no suicidal ideation at baseline (C-SSRS score=0) to any suicidal ideation during treatment (C-SSRS score=1-5): 40 mg, 3.9% (4/103); 80 mg, 0.9% (1/111); PBO, 2.9% (5/174).ConclusionData from 3 double-blind, placebo-controlled trials indicate that once-daily VBZ treatment was not associated with a worsening in depression-related symptoms or an increased risk of suicidal ideation or behavior.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.

ObjectiveTo evaluate the long-term safety and tolerability of once-dailyvalbenazine in adults with tardive dyskinesia(TD).MethodsData were pooled from KINECT 3 (NCT02274558: 6-week double-blind placebo-controlled period, followed by a 42-week double-blind extension and 4-week drug-free washout) and KINECT 4 (NCT02405091: 48-week open-label treatment period and 4-week drug-free washout). KINECT 3/4 study completers could enroll in a subsequent rollover study (NCT02736955: up to 72weeks of open-label treatment or until valbenazine became commercial available); data from this study were described separately for this analysis. Valbenazine dose groups (40 and 80mg) were pooled for analysis. Safety assessments included treatment-emergent adverse events (TEAEs) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Psychiatric status was assessed in KINECT 3 and KINECT 4 using the following measures: Positive and Negative Syndrome Scale (PANSS) total score and Calgary Depression Scale for Schizophrenia (CDSS) in participants with schizophrenia/schizoaffective disorder; Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in participants with a mood disorder.ResultsAnalyses included 304 KINECT 3/4 participants and 160 rollover participants. In KINECT 3/4, the summary of TEAEs was as follows: any TEAE (71.7%), serious TEAE (16.8%), and discontinuation due to TEAE (15.5%). TEAEs reported in ≥5% of all KINECT 3/4 participants were headache (8.9%), urinary tract infection (8.9%), somnolence (7.9%), fatigue (6.3%), dizziness (5.9%), and suicidal ideation (5.6%). The summary of TEAEs from the rollover study was as follows: any TEAE (53.1%), serious TEAE (10.0%), and discontinuation due to TEAE (5.6%). The most common TEAEs in the rollover study were back pain and urinary tract infection (4.4%, each); no TEAE was reported in ≥5% of participants. Minimal changes in psychiatric status were observed in KINECT 3/4, as indicated by mean score changes from baseline to Week 48 in participants with schizophrenia/schizoaffective disorder (PANSS total, –3.2; CDSS total, –0.5) or a mood disorder (MADRS total, 0.3; YMRS total, –1.0). Over one-third of study participants had a lifetime history of suicidal ideation or behavior (KINECT 3/4, 41%; rollover, 38%). Most participants had no C-SSRS suicidal ideation at study baseline; of these, >90% had no emergence of suicidal ideation at any time during the study (KINECT 3/4, 93% [276/296]; rollover, 98% [153/156]).ConclusionsValbenazine was well tolerated and no unexpected safety signals were found in adults who received >1 year of once-daily treatment. Psychiatric stability was maintained, and few participants experienced any emergence of suicidal ideation during the studies despite 35–40% having a lifetime history of suicidality. These results indicate that once-daily valbenazine may be an appropriate treatment for the long-term management of TD.Funding Acknowledgements: Neurocrine Biosciences, Inc.

Study ObjectivesThe approval of valbenazine (INGREZZA; VBZ) for the treatment of tardive dyskinesia (TD) in adults was based on results from double-blind, placebo (PBO)-controlled trials. These studies demonstrated the efficacy of once-daily VBZ based on intent-to-treat analyses. However, because many different types ofpatients can develop TD, subgroup analyses describing treatment outcomes by various patient factors were also conducted.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558), with outcomes analyzed by VBZ dose (80 mg, 40 mg) and PBO. Descriptive analyses conducted using the Abnormal Involuntary Movement Scale (AIMS) total score included: mean change from baseline to Week 6; and AIMS response, defined as 50% improvement from baseline to Week 6. Subgroups were defined as follows: age (ResultsThe pooled population included 373 participants (VBZ 80 mg, n=101; VBZ 40 mg, n=114; PBO, n=158). Mean improvements from baseline to Week 6 in AIMS total score were greater overall with VBZ compared to PBO. Within subgroup categories, AIMS score improvement with VBZ 80 mg (recommended dose) was greater in CYP2D6 PMs (n=17; 80 mg, -6.8; 40 mg, 2.4; PBO, 0.5), participants taking no concomitant antipsychotics (n=64; 80 mg, -4.9; 40 mg, -3.0; PBO, 0.0), and overweight participants (BMI 25 to ConclusionThese preliminary analyses indicate that TD improvements were generally greater with VBZ than PBO across most subgroups. However, the small sizes of some subgroups may need to be considered when interpreting results. Additional analyses within subgroup categories are ongoing and will be presented at the meeting.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.

BackgroundThe efficacy of valbenazine (INGREZZA) in tardive dyskinesia (TD) was demonstrated in placebo-controlled clinical trials, based on the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7). In these trials, mean changes in the AIMS total score were significantly greater with valbenazine 80 mg than with placebo. Currently, no minimal clinically important difference (MCID) has been established for the AIMS total score in patients with TD. Using valbenazine trial data, analyses were conducted to establish a MCID for AIMS total score in TD.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Using the Clinical Global Impression ofChange (CGI-TD) as an anchor comparison, AIMS total score changes from baseline to Week 6 were summarized for all study participants (pooled valbenazine and placebo groups) with a “minimal” CGI-TD score of ≤3 (minimally improved or better) or “robust” ≤2 (much improved or better) at Week 6.ResultsIn the pooled population (N=373), 72% and 29% of all participants had CGI-TD scores of ≤3 and ≤2, respectively. The median (maximum, minimum) change from baseline in AIMS total score at Week 6 was -2 (-13, 8) in participants with CGI-TD score ≤3 and -3 ( 13, 8) in participants with a score ≤2.ConclusionPooled data from 3 randomized, double-blind, placebo-controlled trials suggest that a 2 point decrease in AIMS total score may represent the minimal clinically meaningful improvement. Larger AIMS score improvements were associated with “much improved” or “very much improved” CGI TD assessments.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.