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2 KINECT 2 NCT Baseline Week 2 Week 4 Week 6 Valbenazine mg Valbenazine 40 mg KINECT 3 NCT Valbenazine 80 mg a KINECT 2 and KINECT 3 were 6-week, double-blind placebo-controlled trials of once-daily valbenazine Valbenazine (VBZ) dose groups were pooled for analysis as follows: 40 mg: included 50 mg (KINECT 2) and 40 mg (KINECT 3) 80 mg: included 75 mg (KINECT 2) and 80 mg (KINECT 3) Subjects who received 25 mg in KINECT 2 were excluded from this analysis a Subjects randomized to 80 mg in KINECT 3 were initiated at 40 mg for 1 week. 2

3 Key inclusion criteria: Diagnostic and Statistical Manual of Mental Disorders (e.g., DSM-IV) diagnosis of schizophrenia, schizoaffective disorder, or mood disorder; required to be psychiatrically stable prior to study entry (Brief Psychiatric Rating Scale score <50 at screening) DSM-IV diagnosis of DRBA-induced TD for 3 months prior to screening Moderate or severe TD, as qualitatively assessed by an external reviewer at screening Key exclusion criteria: Active, clinically significant, and unstable medical condition within 1 month prior to screening Comorbid movement disorder more prominent than TD Significant risk for active suicidal ideation, suicidal behavior, or violent behavior Stable doses of concomitant medications to treat psychiatric and medical conditions were allowed throughout the study 3

4 Based on AIMS total score: 10% to 90% improvement from baseline to Week 6 Based on AIMS item scores: improvement from score 2 (mild to severe) at baseline to 1 (minimal to none) at Week 6 All analyses were conducted in psychiatric diagnosis subgroups (i.e., schizophrenia/schizoaffective disorder or mood disorder) Odds ratios (ORs) and numbers needed to treat (NNTs) were estimated for all response analyses; P-values for valbenazine versus placebo were from the chi-square test In both studies, AIMS was scored by consensus between 2 central video raters who were blinded to treatment and study visit 4

5 Within each diagnosis subgroup, baseline characteristics were generally similar across treatment arms Schizophrenia/Schizoaffective Disorder (n=80) Valbenazine 40 mg (n=54) Valbenazine 80 mg (n=70) (n=44) Mood Disorder Valbenazine 40 mg (n=28) Valbenazine 80 mg (n=42) Age, mean (SD), years 56.2 (9.4) 55.5 (8.3) 56.4 (10.1) 56.8 (11.7) 54.9 (8.5) 56.1 (10.6) Male, n (%) 54 (67.5) 34 (63.0) 42 (60.0) 14 (31.8) 12 (42.9) 19 (45.2) Race, n (%) White/Caucasian 36 (45.0) 26 (48.1) 38 (54.3) 36 (81.8) 21 (75.0) 27 (64.3) Black/African-American 38 (47.5) 24 (44.4) 31 (44.3) 7 (15.9) 6 (21.4) 13 (31.0) Other 6 (7.5) 4 (7.4) 1 (1.4) 1 (2.3) 1 (3.6) 2 (4.8) Body mass index, mean (SD), kg/m (5.6) 28.5 (5.4) 27.8 (6.0) 28.4 (4.9) 29.3 (5.7) 28.6 (5.8) TD duration, mean (SD), years 27.1 (13.4) 23.0 (12.7) 25.8 (13.5) 22.0 (13.8) 21.7 (14.1) 17.3 (10.3) AIMS score, mean (SD) Item 1: face 1.0 (1.0) 0.9 (1.0) 1.1 (1.0) 1.2 (1.1) 1.1 (1.0) 1.0 (1.0) Item 2: lips 1.3 (1.0) 1.4 (1.0) 1.5 (1.0) 1.8 (1.0) 1.6 (1.0) 1.5 (0.9) Item 3: jaw 1.6 (1.3) 1.7 (1.2) 1.6 (1.2) 1.6 (1.1) 2.0 (1.3) 1.5 (1.0) Item 4: tongue 1.4 (1.1) 1.6 (1.1) 1.4 (1.1) 1.8 (1.3) 2.4 (0.8) 1.9 (1.0) Item 5: upper extremities 1.3 (0.9) 1.1 (0.9) 1.3 (0.8) 1.4 (1.0) 1.4 (0.7) 1.4 (0.9) Item 6: lower extremities 1.0 (0.9) 1.0 (0.9) 1.3 (0.8) 1.4 (1.0) 1.5 (0.9) 1.4 (1.0) Item 7: trunk 1.1 (1.2) 1.1 (1.3) 1.2 (1.2) 1.1 (1.2) 1.4 (1.3) 1.3 (1.2) Total: sum of items (4.3) 8.8 (4.2) 9.4 (3.6) 10.2 (4.6) 11.4 (3.6) 10.0 (3.7) 40 mg group includes 50 mg (KINECT 2) and 40 mg (KINECT 3); 80 mg group includes 75 mg (KINECT 2) and 80 mg (KINECT 3) AIMS, Abnormal Involuntary Movement Scale; SD, standard deviation; TD, tardive dyskinesia 5

6 Criteria NNT OR (95%CI) 10% 20% 30% (0.8, 3.7) (1.4, 5.7) (0.7, 3.0) (1.4, 5.7) (0.6, 3.0) (1.4, 6.1) Percentage of Subjects 44.3% 37.1% 45.8% 27.1% 33.3% 58.3% 62.3% 52.5% 68.9% Of subjects in both subgroups with available data (baseline and Week 6), AIMS total score response rates at Week 6 were consistently higher with valbenazine (40 and/or 80 mg) relative to placebo In the schizophrenia/schizoaffective disorder subgroup, statistically significant differences between valbenazine 80 mg and placebo were found for AIMS responses of 10% to 80% (ORs >2 and NNTs <10) 40% (0.7,3.8) (1.6, 7.1) 21.4% 31.3% 47.5% 50% (1.1, 7.1) (2.0, 11.2) 12.9% 29.2% * 41.0% * 60% (0.8, 7.4) (1.8, 13.1) 8.6% 18.8% 31.1% 70% 80% (0.6, 11.4) (1.5, 20.4) (0.5, 17.6) (1.6, 35.3) 4.3% 10.4% 2.9% 8.3% 19.7% 18.0% (n=70) Valbenazine 40 mg (n=48) Valbenazine 80 mg (n=61) 90% (0.5, 45.6) (0.7, 54.3) 1.4% 6.3% 8.2% *P<0.05, P<0.01, *P vs placebo AIMS, Abnormal Involuntary Movement Scale; CI, confidence interval; NC, not calculable; NNT, number needed to treat; OR, odds ratio 6

7 Criteria NNT OR (95%CI) 10% 20% 30% (1.2, 10.5) (1.5, 9.8) (1.0, 8.1) (2.5, 17.3) (0.6, 5.7) (1.4, 9.1) Percentage of Subjects 40.5% 26.2% 23.8% 37.5% 50.0% 52.5% 70.8% * 72.5% 70.0% * In the mood disorder subgroup, statistically significant differences between valbenazine 80 mg and placebo were found for AIMS responses of 10% to 60% (ORs >2 and NNTs <10) 40% (0.8, 8.1) (1.5, 11.4) 16.7% 33.3% 45.0% 50% (0.8, 11.0) (1.4, 13.8) 11.9% 29.2% 37.5% 60% (0.7, 15.8) (1.1, 17.1) 7.1% 20.8% 25.0% * 70% 80% (0.2, 13.8) (0.5, 15.7) (0.3, 43.4) (0.2, 24.8) 4.8% 8.3% 12.5% 2.4% 8.3% 5.0% (n=42) Valbenazine 40 mg (n=24) Valbenazine 80 mg (n=40) 90% 24 NC 20 NC 0.0% 4.2% 5.0% *P<0.05, P<0.01, *P vs placebo AIMS, Abnormal Involuntary Movement Scale; CI, confidence interval; NC, not calculable; NNT, number needed to treat; OR, odds ratio 7

8 1: Face 2: Lips 3: Jaw NNT OR (95%CI) n/n 8/ (0.6, 8.4) 9/ (0.4, 5.6) 8/17 12/ (0.5, 4.0) 13/ (0.5, 3.9) 14/29 11/ (0.3, 2.5) 9/ (0.6, 4.7) 13/29 Percentage of Subjects 36.4% 47.1% 40.0% 48.1% 48.3% 32.4% 29.0% 44.8% 56.3% In the schizophrenia/schizoaffective disorder subgroup, a higher proportion of subjects had an item response (score 2 at baseline, score 1 at Week 6) with valbenazine (40 and/or 80 mg) versus placebo in all body regions However, diagnosis subgroups differed in terms of which AIMS items were statistically significant (P<0.05) and clinically meaningful (ORs >2 or NNTs <10) 4: Tongue 10/ (0.8, 6.4) 15/ (0.8, 7.6) 13/ % 53.6% 56.5% 5: Upper Extremities 9/ (0.8, 12.6) 8/ (0.6, 5.2) 12/ % 46.2% 61.5% 6: Lower Extremities 10/ (0.2, 2.7) 7/ (0.4, 3.7) 14/ % 45.5% 50.0% Valbenazine 40 mg 7: Trunk 5/ (0.4, 6.1) 5/ (1.0, 12.4) 12/ % 27.8% Valbenazine 80 mg 48.0% * a Defined as an AIMS item score improvement from 2 at baseline to 1 at Week 6 *P<0.05, *P<0.001 vs placebo. A negative NNT value indicates a lower AIMS response rate with valbenazine vs placebo AIMS, Abnormal Involuntary Movement Scale; CI, confidence interval; n, number of responders; N, number of participants with AIMS item score 2 at baseline; NNT, number needed to treat; OR, odds ratio 8

9 1: Face 2: Lips 3: Jaw NNT OR (95%CI) n/n 3/ (0.5, 18.3) 4/ (0.8, 22.9) 7/13 10/ (0.6, 8.0) 7/ (1.0, 10.1) 14/22 8/ (0.3, 4.2) 5/ (0.9, 10.1) 13/22 Percentage of Subjects 21.4% 44.4% 35.7% 32.0% 33.3% 53.8% 53.8% 63.6% 59.1% * In the mood disorder subgroup, a higher proportion of subjects had an item response (score 2 at baseline, score 1 at Week 6) with valbenazine (40 and/or 80 mg) versus placebo in all body regions However, diagnosis subgroups differed in terms of which AIMS items were statistically significant (P<0.05) and clinically meaningful (ORs >2 or NNTs <10) 4: Tongue 7/ (0.6, 6.6) 9/ (0.4, 4.8) 9/ % 36.0% 42.9% 5: Upper Extremitie s 2/ (0.8, 31.7) 5/ (4.4, 176.8) 14/ % 38.5% 77.8% * 6: Lower Extremitie s 3/ (0.8, 20.3) 6/ (1.0, 19.9) 9/ % 42.9% 45.0% * Valbenazine 40 mg 3/14 7: Trunk (0.4, 12.3) 4/ (0.6, 12.8) 9/ % 36.4% Valbenazine 80 mg 42.9% a Defined as an AIMS item score improvement from 2 at baseline to 1 at Week 6. *P<0.05, *P<0.001 vs placebo A negative NNT value indicates a lower AIMS response rate with valbenazine vs placebo AIMS, Abnormal Involuntary Movement Scale; CI, confidence interval; n, number of responders; N, number of subjects with AIMS item score 2 at baseline; NNT, number needed to treat; OR, odds ratio 9