Mean baseline AIMS scores:
Placebo 9.9, 40 mg 9.8, 80 mg 10.4
Efficacy in adults with tardive dyskinesia
SELECT EFFICACY ENDPOINT:
6-week reductions
48-week reductions
48-week response
Long-term remission
6-week reductions
6-week reductions
48-week reductions
48-week response
Long-term remission
Rapid, robust results. Simply achieved.1-3
REDUCTIONS IN AIMS TOTAL SCORE IN KINECT 3
Mean change in AIMS total score from baseline to Week 61-3
aP≤0.001 vs placebo; adjusted for multiplicity.
Effect size=0.9.
*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.
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; ITT, intent-to-treat; LS mean, least squares mean; SD, standard deviation; SEM, standard error of mean.
KINECT 3 STUDY DESIGN
Sustained reductions. Sustained satisfaction.4-6
REDUCTIONS IN AIMS TOTAL SCORE IN OPEN-LABEL KINECT 4
Mean change in AIMS total score from baseline to Week 48 (site raters)4,5,*
Mean baseline AIMS scores: 40 mg 14.2, 80 mg 15.0
Patients in KINECT 4 followed a different dosing schedule than KINECT 3 pivotal study. See “KINECT 4 STUDY DESIGN” for additional detail.
*Data not shown for 11 patients who had a dose reduction from 80 mg to 40 mg after Week 4.
†(n/N=55/56). In rollover study of patients who completed KINECT 3 and KINECT 4 studies. Analysis at baseline and for completers of rollover study.
KINECT 4 STUDY DESIGN
DOWNLOAD THE REPRINTS FOR MORE RESULTS FROM KINECT 4
Clinically meaningful improvements—early and over time7
TREATMENT RESPONSE IN OPEN-LABEL KINECT 4
MCID in AIMS total score through Week 48 (completers; n=103)7
Minimal clinically important difference (MCID) established by the TD Working Group of key opinion leaders in psychiatry and neurology.8
A ≥2-point decrease in AIMS corresponds to symptoms reported “minimally to very much improved” on Patient Global Impression of Change and Clinical Global Impression of Change scales.8
Post hoc analysis of KINECT 4 completers taking INGREZZA (40 mg and 80 mg). Results are descriptive.
Patients in KINECT 4 followed a different dosing schedule than KINECT 3 pivotal study. See “KINECT 4 STUDY DESIGN” for additional detail.
KINECT 4 STUDY DESIGN
DOWNLOAD THE REPRINTS FOR MORE RESULTS FROM KINECT 4
More than reductions. Achieve remission with INGREZZA.4,7,8
TD REMISSION IN OPEN-LABEL KINECT 4
Patients with ≤1 on each AIMS item 1–7 at Week 484,7,8
REMISSION IN TD4,8
No or minimal involuntary movements (≤1 on each AIMS item 1–7)
- Muscles of facial expression
- Lips and perioral area
- Jaw
- Tongue
- Upper extremities
- Lower extremities
- Trunk
KINECT 4 STUDY DESIGN
Post hoc analysis of KINECT 4 completers taking INGREZZA (40 mg and 80 mg).
Results are descriptive.
Remission defined as "complete response" by study authors.
Patients in KINECT 4 followed a different dosing schedule than KINECT 3 pivotal study. See “KINECT 4 STUDY DESIGN” for additional detail.
DOWNLOAD THE REPRINTS FOR MORE RESULTS FROM KINECT 4
Watch expert perspective videos on INGREZZA
Featuring Amy LaCouture, RN, BSN, PMHNP-BC
These videos were sponsored and developed by Neurocrine Biosciences.
The speaker is a paid consultant of Neurocrine Biosciences.
Why I choose INGREZZA for my adult patients with tardive dyskinesia (TD)
Case study: John, a patient with schizophrenia and tardive dyskinesia (TD)
THERAPEUTIC DOSE FROM DAY 1
The only VMAT2 inhibitor that offers an effective starting dosage you can adjust based on response and tolerability1
DOSING INFOSEE REAL-WORLD RESULTS
WITH INGREZZA
View videos of real-world patients with TD treated with INGREZZA
CASE VIDEOS
INGREZZA CLINICAL
SAFETY DATA
INGREZZA was studied across a broad range of TD patients
SAFETY PROFILEREFERENCES:
- INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc.
- Nguyen HQ, Kuan HS, Crass RL, et al. A model-informed drug development approach supporting the approval of an unstudied valbenazine dose for patients with tardive dyskinesia. J Clin Psychopharmacol. Published online July 25, 2024.
- Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
- Data on file. Neurocrine Biosciences, Inc.
- Marder SR, Singer C, Lindenmayer JP, et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol. 2019;39(6):620-627.
- Lindenmayer J-P, Verghese C, Marder SR, et al. A long-term, open-label study of valbenazine for tardive dyskinesia. CNS Spectr. 2021;26(4):345-353.
- Correll CU, Citrome L, Singer C, et al. Sustained treatment response and global improvements with long-term valbenazine in patients with tardive dyskinesia. J Clin Psychopharmacol. 2024;44(4):353-361.
- Correll CU, Cutler AJ, Kane JM, McEvoy JP, Liang GS, O’Brien CF. Characterizing treatment effects of valbenazine for tardive dyskinesia: additional results from the KINECT 3 Study. J Clin Psychiatry. 2018;80(1):18m12278.
- Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: Results of the 1-year KINECT 3 extension study. J Clin Psychiatry. 2017;78(9):1344-1350.
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules and INGREZZA® SPRINKLE (valbenazine) capsules are indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA and INGREZZA SPRINKLE, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
CONTRAINDICATIONS
INGREZZA and INGREZZA SPRINKLE are contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA or INGREZZA SPRINKLE.
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including cases of angioedema involving the larynx, glottis, lips, and eyelids, have been reported in patients after taking the first or subsequent doses of INGREZZA. Angioedema associated with laryngeal edema can be fatal. If any of these reactions occur, discontinue INGREZZA or INGREZZA SPRINKLE.
Somnolence and Sedation
INGREZZA and INGREZZA SPRINKLE can cause somnolence and sedation. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA or INGREZZA SPRINKLE.
QT Prolongation
INGREZZA and INGREZZA SPRINKLE may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA and INGREZZA SPRINKLE should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission, including INGREZZA. The management of NMS should include immediate discontinuation of INGREZZA or INGREZZA SPRINKLE, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems. If treatment with INGREZZA or INGREZZA SPRINKLE is needed after recovery from NMS, patients should be monitored for signs of recurrence.
Parkinsonism
INGREZZA and INGREZZA SPRINKLE may cause parkinsonism. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA or INGREZZA SPRINKLE treatment in patients who develop clinically significant parkinson-like signs or symptoms.
ADVERSE REACTIONS
The most common adverse reaction in patients with tardive dyskinesia (≥5% and twice the rate of placebo) is somnolence.
The most common adverse reactions in patients with chorea associated with Huntington’s disease (≥5% and twice the rate of placebo) are somnolence/lethargy/sedation, urticaria, rash, and insomnia.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.
Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules.
Please see full Prescribing Information, including Boxed Warning.
+Expand-Collapse
Important Safety Information
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA, can increase the risk of depression and suicidal thoughts and
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules and INGREZZA® SPRINKLE (valbenazine) capsules are indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA and INGREZZA SPRINKLE, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules and INGREZZA® SPRINKLE (valbenazine) capsules are indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA and INGREZZA SPRINKLE, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
CONTRAINDICATIONS
INGREZZA and INGREZZA SPRINKLE are contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA or INGREZZA SPRINKLE.
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including cases of angioedema involving the larynx, glottis, lips, and eyelids, have been reported in patients after taking the first or subsequent doses of INGREZZA. Angioedema associated with laryngeal edema can be fatal. If any of these reactions occur, discontinue INGREZZA or INGREZZA SPRINKLE.
Somnolence and Sedation
INGREZZA and INGREZZA SPRINKLE can cause somnolence and sedation. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA or INGREZZA SPRINKLE.
QT Prolongation
INGREZZA and INGREZZA SPRINKLE may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA and INGREZZA SPRINKLE should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission, including INGREZZA. The management of NMS should include immediate discontinuation of INGREZZA or INGREZZA SPRINKLE, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems. If treatment with INGREZZA or INGREZZA SPRINKLE is needed after recovery from NMS, patients should be monitored for signs of recurrence.
Parkinsonism
INGREZZA and INGREZZA SPRINKLE may cause parkinsonism. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA or INGREZZA SPRINKLE treatment in patients who develop clinically significant parkinson-like signs or symptoms.
ADVERSE REACTIONS
The most common adverse reaction in patients with tardive dyskinesia (≥5% and twice the rate of placebo) is somnolence.
The most common adverse reactions in patients with chorea associated with Huntington’s disease (≥5% and twice the rate of placebo) are somnolence/lethargy/sedation, urticaria, rash, and insomnia.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.
Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules.
Please see full Prescribing Information, including Boxed Warning.
KINECT® 3: INGREZZA pivotal study design1-4
Study overview
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.3,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.3,9,b
60 mg data modeling2
Based on modeling and simulation of data derived from previous INGREZZA clinical studies under Model-Informed Drug Development (MIDD) regulatory path.
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.9
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 52.3,4,9
| a | Patients randomized to 80 mg started on 40 mg for 1 week. |
| b | Safety population. |
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout. |
Study endpoints
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 process3
Secondary efficacy endpoint
- The key secondary endpoint was the mean Clinical Global Impression of Change scale for Tardive Dyskinesia (CGI-TD) score compared to placebo3
- CGI-TD is a clinician-rated scale used to assess the overall global improvement of TD on a 7-point Likert scale (ranged 1 [very much improved] to 7 [very much worse])3
Statistical analysis
- 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)2
- 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 data2
- 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 used3
- 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 sequence1,3:
- 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
Study population
-
Enrolled patients:
- 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 collected1,3
- 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder
- 34% (77/227) of patients had mood disorder
KINECT® 4: INGREZZA long-term study design4
Study overview
aPostbaseline visits during OL treatment period were at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48.
BL, baseline; OL, open-label; DFWO, drug-free washout.
Patients who received 80 mg in the KINECT 4 study followed a different dosing schedule than those in the KINECT 3 pivotal study. In KINECT 3, patients had a dose increase from 40 mg to 80 mg after Week 1. In KINECT 4, patients had a dose increase from 40 mg to 80 mg after Week 4, based on CGI-TD score of ≥3 and acceptable safety and tolerability of 40 mg. The impact of this on long-term effectiveness is not known.
KINECT 4 was a phase 3, multicenter, open-label, fixed-dose escalation study to evaluate the long-term safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily. Long-term effectiveness of INGREZZA was also assessed.4
The study included 167 medically stable patients with a clinical diagnosis of schizophrenia, schizoaffective disorder, or mood disorder with moderate or severe DRBA-induced TD: 73% (119/163) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder; 27% (44/163) of patients had a mood disorder.4
All patients received INGREZZA 40 mg for 4 weeks. The dosage was then escalated to 80 mg once daily based on individual patient tolerability and clinical response to be reflective of real-world care.4
- At the end of Week 4 (first postbaseline visit), patients were escalated to 80 mg if both of the following conditions were met4:
- (1) Clinical Global Impression of Change-TD (CGI-TD) score of ≥3 and
- (2) acceptable safety and tolerability with 40 mg, based on investigator’s judgment
- A dose reduction to 40 mg was permitted once any time after dose escalation due to tolerability. Patients were discontinued if the 40 mg dose was not tolerated4