Efficacy in adults with tardive dyskinesia

INGREZZA reduced tardive dyskinesia (TD) severity at 6 weeks, with results you can start to see as early as 2 weeks1-3

LS mean change from baseline in AIMS dyskinesia total score through 6 weeks (ITT population)1-3

6-week primary endpoint graphReductions in tardive dyskinesia INGREZZA (valbenazine) capsules –0.1(n=69) -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 –0.3(n=76) –1.9 (n=77) –1.8* –0.1(n=73) –1.4(n=64) –2.4* –2.7(n=73) –1.9(n=63) –3.2(n=70)a –2.7* BL WEEK 2 WEEK 4 WEEK 6 Placebo (n=76) INGREZZA 40 mg (n=70) INGREZZA 80 mg (n=79) INGREZZA 60 mg* (modeled) L S M E A N C H A NG E F R OM B L ( S E M ) 0.0 0.5 –0.5 –1.0 –1.5 –3.5 –4.0 –2.0 –2.5 –3.0 –1.4 (n=70) 6-week primary endpoint graphReductions in tardive dyskinesia INGREZZA (valbenazine) capsules -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 Placebo (n=76) INGREZZA 40 mg (n=70) INGREZZA 60 mg* (modeled) INGREZZA 80 mg (n=79)

*Based on modeling and simulation. The LS mean is adjusted for baseline AIMS score and disease category and is shown for consistency with 40 mg and 80 mg observed values from the KINECT 3 study.

a P≤0.001 dose that was statistically significantly different from placebo to control for multiple comparisons.

Mean baseline AIMS score (SD): placebo 9.9 (4.3), 40 mg 9.8 (4.1), 80 mg 10.4 (3.6).

~30% reduction in TD severity at 6 weeks with INGREZZA® (valbenazine) capsules 80 mg1-3,†

† In a post hoc analysis of the primary efficacy endpoint of patients randomized to INGREZZA 80 mg at baseline through Week 6.

AIMS, Abnormal Involuntary Movement Scale; BL, baseline; ITT, intent-to-treat; LS mean, least squares mean; SD, standard deviation;
SEM, standard error of mean.

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~70% of patients on INGREZZA 80 mg saw reductions in their uncontrolled movements1,3,*

Percent of patients with specified magnitude of AIMS total score improvement at the end of Week 61,3,*

6-week responses graphMagnitude of improvement in AIMS with INGREZZA (valbenazine) capsules PERCENTAGE (%) 55 60 50 45 40 5 0 35 30 25 20 15 10 NO CHANGE OR WORSENED 1 TO 2 3 TO 4 5 TO 6 7 TO 8 9 TO 13 MAGNITUDE OF IMPROVEMENT FROM BASELINE IN AIMS DYSKINESIA TOTAL SCORE INGREZZA 80 mg (n=70) INGREZZA 40 mg (n=63) Placebo (n=69) 58% 38% 29% 23% 24% 14% 10% 16% 14% 4% 10% 20% 4% 3% 16% 0% 10% 7% 57% ≥3-point improvement on 80 mg 71% ≥1-point improvement on 80 mg 6-week responses graphMagnitude of improvement in AIMS with INGREZZA (valbenazine) capsules 55 60 50 45 40 35 30 25 20 15 10 5 0 NO CHANGE OR WORSENED 1 to 2 3 to 4 5 to 6 7 to 8 9 to 13 71% ≥1-point improvement on 80 mg 57% ≥3-point improvement on 80 mg 9 to 13 7 to 8 5 to 6 3 to 4 1 to 2 No change or worsened 0% 4% 4% 10% 23% 58% 10% 3% 10% 16% 24% 38% 7% 16% 20% 14% 14% 29% PLACEBO 80 mg 40 mg MAGNITUDE OF IMPROVEMENT FROM BASELINE IN AIMS DYSKINESIA TOTAL SCORE Placebo (n=69) INGREZZA 40 mg (n=63) INGREZZA 80 mg (n=70) MAGNITUDE OF IMPROVEMENT FROM BASELINE IN AIMS DYSKINESIA TOTAL SCORE PERCENTAGE (%)—SEE BELOW FOR DETAILED DATA PERCENTAGE (%) OF PATIENTS

*Post hoc analysis included patients who had a baseline and a Week 6 AIMS total score. Reduction in uncontrolled movements as assessed by ≥1-point decrease in AIMS total score.

Mean baseline AIMS score (SD): placebo 9.9 (4.3), 40 mg 9.8 (4.1), 80 mg 10.4 (3.6).

AIMS, Abnormal Involuntary Movement Scale; SD, standard deviation.

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Treat TD first line with INGREZZA

Review expert recommendations for the treatment of tardive dyskinesia in adults.

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INGREZZA provided continued reduction of TD severity through 48 weeks1,4

Extension study of INGREZZA 40 mg and INGREZZA 80 mg (ITT population)1,3,4

48-week endpoint graphLong-term reductions in tardive dyskinesia with INGREZZA (valbenazine) capsules AIMS MEAN SCORE CHANGE FROM BL 1.0 0.0 –1.0 –2.0 –6.0 –7.0 –3.0 –4.0 –5.0 –1.3 (n=32) –1.8 (n=29) –2.5 (n=50) –4.2(n=31) –4.3(n=58) –2.2 (n=59) –3.5(n=33) –4.2(n=67) –2.5 (n=37) –4.8(n=27) –5.0(n=50) –2.3(n=27) –2.9(n=24) –0.1(n=41) –1.1(n=34) –1.4(n=24) –3.5(n=22) –3.0(n=34) –4.4(n=43) –5.5(n=22) BASELINE to WEEK 8 WEEK 16 WEEK 32 WEEK 48 End of Extension End of DFWO End of DBPC: WEEK 6 WEEK 52 Placebo(Week 6 n=69) INGREZZA 40 mg(Week 6 n=63) Re-randomized toINGREZZA 40 mg INGREZZA 80 mg(Week 6 n=70) Re-randomized toINGREZZA 80 mg 48-week endpoint graphLong-term reductions in tardive dyskinesia with INGREZZA (valbenazine) capsules –0.1 –1.1 –3.5 –1.4 –2.9 –3.0 –5.5 –4.4 –2.3 –2.5 –4.8 –5.0 –4.3 –4.2 –2.5 –1.8 –1.3 –2.2 –3.5 –4.2 End ofDBPC WEEK End of Extension End of DFWO BL 2 4 8 6 16 32 48 52 1.0 0.0 –1.0 –5.0 –6.0 –2.0 –7.0 –3.0 –4.0 AIMS MEAN SCORE CHANGE FROM BL Re-randomized to INGREZZA 80 mg Re-randomized to INGREZZA 40 mg INGREZZA 80 mg INGREZZA 40 mg Placebo 22 24 41 34 WEEK 52 WEEK 16 WEEK 8 WEEK 6 NUMBER OF PATIENTS 22 24 43 34 WEEK 48 27 31 33 27 29 32 70 50 58 67 63 37 50 59 69 WEEK 32 Placebo INGREZZA 40 mg INGREZZA 80 mg Re-randomized to INGREZZA 40 mg Re-randomized to INGREZZA 80 mg

~39% reduction in TD severity with INGREZZA 80 mg at 48 weeks1,4,*

*In a post hoc analysis that included patients randomized to INGREZZA 80 mg at baseline and those who were re-randomized to INGREZZA 80 mg at Week 6.

AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat.

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See more results for INGREZZA

See why treatment with INGREZZA 40 mg may be appropriate for some patients.a Review results of KINECT 4 study—a phase 3, 1-year, open-label study evaluating long-term treatment with INGREZZA.5

aRecommended dosage is 80 mg once daily, but patients may be maintained or adjusted back to 40 mg based on individual treatment needs.

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Not actual size.

The simple one-capsule, once-daily choice
for your patients with tardive dyskinesia1

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KINECT 3: INGREZZA pivotal study design1-4

Primary efficacy endpoint was mean change from baseline in AIMS dyskinesia total score at Week 6 for 80 mg compared to placebo1

KINECT 3 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of INGREZZA 40 mg and 80 mg, administered once daily, compared to placebo.2,a

The study included 234 medically stable patients with a clinical diagnosis of schizophrenia, schizoaffective disorder, or mood disorder with moderate to severe DRBA-induced TD: 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder; 34% (77/227) of patients had mood disorder.2,4,b

Extension study (6 to 52 weeks)

The INGREZZA extension study evaluated the safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily.4

The 6-week DBPC study period was followed by a double-blind INGREZZA extension period for 42 weeks (total treatment period 48 weeks). At the end of Week 6 (end of the DBPC treatment period), patients were re-consented to confirm their willingness to continue in the study. Patients initially randomized to placebo were re-randomized (1:1) to receive either 40 mg or 80 mg INGREZZA, and patients initially randomized to INGREZZA continued their current dose. Patients re-randomized to 80 mg started on 40 mg for 1 week. Patients then entered a 4-week posttreatment period with a final study visit at the end of Week 52.2-4

aPatients randomized to 80 mg started on 40 mg for 1 week.

bSafety population.

AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout; DRBA, dopamine receptor blocking agent.

Primary endpoint

  • The primary efficacy endpoint was the mean change from baseline (CFB) at the end of Week 6 in the Abnormal Involuntary Movement Scale (AIMS) dyskinesia total score for INGREZZA 80 mg compared to placebo1
  • The AIMS video recordings at baseline and throughout the study were reviewed at each study visit and scored by blinded, central AIMS video raters who scored the AIMS dyskinesia total score (sum of Items 1–7 on AIMS) using a triple-blind consensus scoring process2

Secondary efficacy endpoint

  • The key secondary endpoint was the mean Clinical Global Impression of Change scale for Tardive Dyskinesia (CGI-TD) score compared to placebo2
  • CGI-TD is a clinician-rated scale used to assess the overall global improvement of TD on a 7-point scale (ranged 1 [very much improved] to 7 [very much worse])2
  • The primary efficacy analysis set was the intent-to-treat (ITT) analysis set, which included all patients in the safety analysis set who had a baseline (Day –1) AIMS dyskinesia total score value and at least one postbaseline AIMS dyskinesia total score value reported during the double-blind, placebo-controlled treatment period (ie, after randomization through Week 6 of the study)3
  • Patients who discontinued from the study prior to the scheduled Week 2 visit should have had AIMS data for the early termination (ET) visit, and were therefore expected to be included in this analysis set (the ET visit data in this case was treated as Week 2 data). The ITT analysis set was used for summaries and analyses of efficacy data3
  • In order to control the family-wise error rate for the AIMS and CGI-TD endpoints, as well as for the 2 INGREZZA treatment group comparisons to placebo, a fixed-sequence testing procedure was used2
  • The sequence of tests that were performed at Week 6 is summarized, in order, below. For each endpoint, a P value of ≤0.05 was required to continue the test sequence2,3:
  • AIMS dyskinesia total score mean CFB: INGREZZA 80 mg treatment group vs placebo treatment group
  • CGI-TD mean score: INGREZZA 80 mg treatment group vs placebo treatment group
  • AIMS dyskinesia total score mean CFB: INGREZZA 40 mg treatment group vs placebo treatment group
  • CGI-TD mean score: INGREZZA 40 mg treatment group vs placebo treatment group
  • Enrolled patients2:
  • 234 medically stable males and females
  • Aged 18 to 85
  • Clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced TD or mood disorder with neuroleptic-induced TD (based on the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders [DSM–IV])
  • During the 6-week study period, 2 patients withdrew (1 patient in the placebo group and 1 patient in the INGREZZA 40 mg group), and 5 patients had no postbaseline safety data collected1,2
  • 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder
  • 34% (77/227) of patients had mood disorder

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