Safety profile in tardive dyskinesia

In clinical trials, INGREZZA was generally well tolerated across a broad
range of adult tardive dyskinesia (TD) patients1,2

COMBINED SAFETY ACROSS 3 KEY STUDIES

Adverse reactions in 3 placebo-controlled studies of a 6-week treatment duration reported at ≥2% and >placebo (safety population)1

Adverse
Reaction
INGREZZA
(n=262) (%)
Placebo
(n=183) (%)
Somnolence 10.9% 4.2%
Anticholinergic effects 5.4% 4.9%
Balance disorders/fall 4.1% 2.2%
Headache 3.4% 2.7%
Akathisia 2.7% 0.5%
Vomiting 2.6% 0.6%
Nausea 2.3% 2.1%
Arthralgia 2.3% 0.5%

Discontinuation due to adverse reactions was 3% with INGREZZA® (valbenazine) capsules vs 2% with placebo1

Patients in the clinical trials were allowed to remain on their stable psychiatric treatment regimen1:

85%

took second-generation antipsychotics

27%

took first-generation antipsychotics

ADVERSE REACTIONS BY DOSE IN KINECT 3

Treatment-emergent adverse reactions with incidence ≥2% in all patients treated with INGREZZA and at a higher incidence than placebo during the 6-week treatment period in a pivotal study (safety population)2

Adverse
Reaction
All
INGREZZA
treated

(n=151) (%)
INGREZZA
40 mg

(n=72) (%)
INGREZZA
80 mg

(n=79) (%)
Placebo
(n=76) (%)
Overall 45.7% 40.3% 50.6% 43.4%
Somnolence 5.3% 5.6% 5.1% 3.9%
Akathisia 3.3% 4.2% 2.5% 1.3%
Dry mouth 3.3% 6.9% 0.0% 1.3%
Arthralgia 2.6% 1.4% 3.8% 1.3%
Dyskinesia 2.0% 0.0% 3.8% 0.0%
Vomiting 2.0% 0.0% 3.8% 0.0%
Anxiety 2.0% 1.4% 2.5% 0.0%
Fatigue 2.0% 2.8% 1.3% 1.3%
Weight increase 2.0% 1.4% 2.5% 0.0%
Insomnia 2.0% 1.4% 2.5% 1.3%

The most common types of concomitant medications were2,3:

  • Antipsychotics (85.5%)
  • Antidepressants (66.5%)
  • Anticholinergics (37.0%)
  • Antiepileptics (35.2%)
  • Anxiolytics (27.7%)
  • ACE inhibitors (25.1%)

PSYCHIATRIC STATUS GENERALLY REMAINED STABLE DURING THE KINECT 3 STUDY2

Safety assessments of psychiatric disorders from baseline through 6 weeks3

Disorder Mean score
increased
or worsened
Measure
Schizophrenia No PANSSa
Mania No YMRSb
Suicidal ideation/
behavior
No C-SSRSc
Depression No CDSS,d MADRSe
a

Mean change in Positive and Negative Syndrome Scale (PANSS) total score from baseline at 6 weeks was −0.4 for INGREZZA 40 mg, −0.8 for INGREZZA 80 mg, and ±0.0 for placebo.

b

Mean change in Young Mania Rating Scale (YMRS) total score from baseline at 6 weeks was −0.4 for INGREZZA 40 mg, −1.4 for INGREZZA 80 mg, and +0.5 for placebo.

c

Incidence of suicidal ideation or behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) was 5.6% for INGREZZA 40 mg, 2.5% for INGREZZA 80 mg, and 5.3% for placebo.

d

Mean change in Calgary Depression Scale for Schizophrenia (CDSS) total score from baseline at 6 weeks was −0.5 for INGREZZA 40 mg, −0.4 for INGREZZA 80 mg, and −0.1 for placebo.

e

Mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline at 6 weeks was ±0.0 for INGREZZA 40 mg, −1.5 for INGREZZA 80 mg, and +1.2 for placebo.

Drug-induced parkinsonism across the study period, as measured by the Simpson-Angus Scale3

In the 3 placebo-controlled clinical studies in patients with TD, the incidence of parkinson-like adverse events was 3% of patients treated with INGREZZA and <1% of patients treated with placebo. The mean change in Simpson-Angus Scale score from baseline at 6 weeks across studies was1,3,f:

  • 0.0 for INGREZZA 40 mg
  • −0.1 for INGREZZA 80 mg
  • −0.1 for placebo
f 40 mg data include doses of 40 mg and 50 mg; 80 mg data include doses of 75 mg and 80 mg.

See long-term safety and tolerability with INGREZZA

Review results of the KINECT 4 study—a phase 3, long-term, open-label study evaluating the safety and tolerability of once-daily INGREZZA.4

DOWNLOAD SUMMARY DOWNLOAD REPRINT

REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc. 2. 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. 3. Data on file. Neurocrine Biosciences, Inc. 4. 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.

Important Information

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS & PRECAUTIONS

Somnolence

INGREZZA can cause somnolence. 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.

QT Prolongation

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA 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.

Parkinsonism

INGREZZA may cause parkinsonism in patients with tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >Placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

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.

Please see INGREZZA full Prescribing Information

Indication and Important Safety Information

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA.

+Expand-Collapse

Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

Important Information

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS & PRECAUTIONS

Somnolence

INGREZZA can cause somnolence. 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.

QT Prolongation

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA 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.

Parkinsonism

INGREZZA may cause parkinsonism in patients with tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >Placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

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.

Please see INGREZZA full Prescribing Information

EXPAND FOR
GUIDELINES

INGREZZA is a recommended first-line TD treatment option.

See guidelines and recommendations