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INGREZZA® (valbenazine) capsules

Mechanism of action and pharmacology of INGREZZA

INGREZZA is a uniquely selective VMAT2 inhibitor1,2

Tardive dyskinesia (TD)

Tardive dyskinesia

Huntington's disease (HD) Chorea

HD chorea

TD—an often persistent movement disorder induced by prolonged DRBA exposure4

TD Mechanism of Disease
  • 1 VMAT2 plays a key role in dopamine signaling2
    • VMAT2 is a transporter protein found in presynaptic neurons of the CNS
    • VMAT2 packages monoamines (eg, dopamine) for release into the synaptic cleft
  • 2 TD is associated with prolonged exposure to DRBAs, including antipsychotics4
  • 3 Prolonged exposure to DRBAs can cause hypersensitivity in postsynaptic dopamine D2 receptors in areas that control motor function2

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

MOA of INGREZZA® (valbenazine) capsules

TD Mechanism of Action
  • 1Selective inhibition of VMAT2 in presynaptic neurons, with no appreciable binding affinity for VMAT1, dopaminergic receptors, or serotonergic receptors2
  • 2INGREZZA is believed to provide reversible reductions of dopamine release into the synaptic cleft2
  • 3INGREZZA is believed to reduce the amount of dopamine available to hypersensitive postsynaptic dopamine D2 receptors1,2

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

Neurodegeneration in the striatum leads to increased dopamine signaling that results in chorea5

HD Chorea Mechanism of Disease

DOPAMINE SIGNALING CYCLE:

  • 1 Dopamine is taken up into the cytosol of the presynaptic neuron through the DA transporter5
  • 2 Here, it is packaged into vesicles by VMAT2 or quickly broken down by enzymes5
  • 3 When the neuron is activated, vesicles full of dopamine fuse with the presynaptic membrane and dopamine is released into the synapse6

VMAT2, vesicular monoamine transporter 2.

Only INGREZZA® (valbenazine) capsules selectively inhibits VMAT2 to counteract increased dopamine signaling7,8

HD Chorea Mechanism of Action

HYPOTHETICAL DOPAMINE SIGNALING CYCLE WITH INGREZZA9

While the mechanism of action of INGREZZA is unclear, it is believed that:

  • 1 Dopamine is taken up into the cytosol of the presynaptic neuron through the DA transporter
  • 2 With INGREZZA blocking VMAT2, less dopamine is packaged into vesicles, and free dopamine is quickly broken down into the cytosol
  • 3 When the neuron is activated, vesicles with less dopamine fuse with the presynaptic membrane, reducing dopamine release into the synapse

VMAT2, vesicular monoamine transporter 2.

ONLY INGREZZA IS UNIQUELY SELECTIVE FOR VMAT2

When all you want is VMAT2 inhibition, all you need is INGREZZA. Only INGREZZA exclusively delivers one primary metabolite (+ α) for potent and selective inhibition of VMAT21-3,*

View full transcript
The Pharmacology of INGREZZA® (valbenazine) capsules, video
*

Based on in vitro VMAT2 binding affinity of dihydrotetrabenazine (HTBZ) metabolites and the primary active metabolite of INGREZZA, + α HTBZ. The clinical significance of in vitro data is unknown and is not meant to imply clinical outcomes.

Only INGREZZA: 100% on-target activity at VMAT23,7,8

Targeting VMAT2 with 100% of the highly selective + α metabolite3,7,8

VMAT2 isomer percentages
INGREZZA, Tetrabenazine, & Deutetrabenazine to isomer, chart

aData from single-center, phase 1, open-label crossover study following single dose of valbenazine 40 mg or deutetrabenazine 24 mg (n=18).7

bData determined in serum sample following tetrabenazine 25 mg (n=1).8

The clinical implications of in vitro data are unknown. These data do not imply superiority in efficacy or safety of any compound.

cAUSTEDO® and AUSTEDO XR® are trademarks of Teva Pharmaceutical Industries Ltd.

The primary metabolite of INGREZZA—+ α—has high affinity for VMAT2 and no appreciable
binding for off-target receptors3,7,8,10

Binding affinity, chart
Binding affinity, chart

dIn vitro data from 2 separate studies. All assays were performed in 1 to 3 independent experiments and in duplicate or triplicate.3,7

eData from single-center, phase 1, open-label crossover study following single dose of valbenazine 40 mg or deutetrabenazine 24 mg (n=18).7

The clinical implications of in vitro data are unknown. These data do not imply superiority in efficacy or safety of any compound.

fAUSTEDO® and AUSTEDO XR® are trademarks of Teva Pharmaceutical Industries Ltd.

THERAPEUTIC DOSE
FROM DAY 1

The only VMAT2 inhibitor that offers an effective starting dosage you can adjust based on response and tolerability1

DOSING INFO

TREAT FIRST LINE WITH
VMAT2 INHIBITORS

VMAT2 inhibitors, like INGREZZA, are recommended as first-line treatment for TD11-13

TD GUIDELINES

REFERENCES:

  1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc.
  2. Harriott ND, Williams JP, Smith EB, Bozigian HP, Grigoriadis DE. VMAT2 inhibitors and the path to INGREZZA (valbenazine). Prog Med Chem. 2018;57(1):87-111.
  3. Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. J Pharmacol Exp Ther. 2017;361(3):454-461.
  4. 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.
  5. Coppen EM, Roos RA. Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs. 2017;77(1):29-46.
  6. Vesicular monoamine transporter 2 (VMAT2) inhibitors. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Accessed March 10, 2023. https://www.ncbi.nlm.nih.gov/books/NBK548187/?report=reader.
  7. Brar S, Vijan A, Scott FL, et al. Pharmacokinetic and pharmacologic characterization of the dihydrotetrabenazine isomers of deutetrabenazine and valbenazine. Clin Pharmacol Drug Dev. 2023;12(4):447-456.
  8. Skor H, Smith EB, Loewen G, O’Brien CF, Grigoriadis DE, Bozigian H. Differences in dihydrotetrabenazine isomer concentrations following administration of tetrabenazine and valbenazine. Drugs R D. 2017;17(3):449-459.
  9. Stahl SM. Comparing pharmacologic mechanism of action for the vesicular monoamine transporter 2 (VMAT2) inhibitors valbenazine and deutetrabenazine in treating tardive dyskinesia: does one have advantages over the other? CNS Spectr. 2018;23(4):239-247.
  10. Data on file. Neurocrine Biosciences, Inc.
  11. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association Publishing, 2020.
  12. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018;389:67-75.
  13. Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020;81(2):19cs12983.

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.

The pharmacology of INGREZZA® (valbenazine) capsules

>>The pharmacology of INGREZZA® (valbenazine) capsules

[On-screen text reads, “The pharmacology of INGREZZA (valbenazine) capsules.”]

>>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.

>>Please see additional Important Safety information at the end of this video.

>>VMAT2 is a proven target when it comes to treating tardive dyskinesia and Huntington’s disease chorea.

[Animation of a target slides into frame. The target reads, “VMAT2.” Footnote at the bottom of the screen reads, “The mechanism of action of INGREZZA is unclear, but is believed to be mediated through the selective inhibition of VMAT2.”]

>>And INGREZZA is a treatment with a precise focus on VMAT2.

[The INGREZZA logo appears on the screen.]

>>As a uniquely selective treatment…

[The INGREZZA logo fades away and transitions to become the tip of an arrow placed within a bow. Text next to bow and arrow reads, “Uniquely selective.” Footnote at the bottom of the screen reads, “Based on in vitro data. The clinical significance of in vitro data is unknown and is not meant to imply clinical outcomes.”]

>>…INGREZZA is metabolized into a single primary metabolite, + alpha.

[Animation zooms in on pink arrowhead, labeled with a + alpha symbol.]

>>The + alpha metabolite has high affinity and selectivity for VMAT2 with no appreciable off-target affinity.

[Animation of arrow launches across the frame. Footnote at the bottom of the screen reads, “Based on in vitro VMAT2 binding affinity of dihydrotetrabenazine (HTBZ) metabolites and INGREZZA’s primary active metabolite, + alpha HTBZ. The clinical significance of in vitro data is unknown and is not meant to imply clinical outcomes.”]

>>With 100% aimed at VMAT2...

[Multiple INGREZZA arrows hit the target’s bullseye labeled, “VMAT2.”]

>>...INGREZZA is targeted where it matters.

[The INGREZZA arrows remain on the VMAT2 target.]

>>Other VMAT2 inhibitors…

[Two quivers filled with arrows appear on screen. One is labeled “Tetrabenazine,” and the other is labeled “Deutetrabenazine.”]

>>…are converted into 4 isomers.

[Animation focuses in on the deutetrabenazine-filled quiver. Four arrows lift out of the quiver.]

>>The most abundant isomer of deutetrabenazine has appreciable affinity for off-target receptors and negligible affinity for VMAT2.

[The isomer arrows pull completely out of the quiver, which leaves the frame. Once out of the quiver, the four arrows stack up vertically. The top arrow is orange and labeled – alpha followed by 66%; the second is purple and labeled + beta followed by 29%; the third arrow is blue color and labeled – beta followed by 3%; the fourth arrow is red and labeled + alpha followed by 2%.]

[Animation of the four different colored arrows fly across the screen. The number of each type of arrow is in relative proportion to the percentages labeled in the previous screen.]

[All arrows fly toward a target labeled VMAT2, but most do not hit the target—only one red arrow and three purple arrows. Footnote at the bottom of the screen reads, “The activity of these compounds is based on in vitro data and the clinical implications are unknown. These data do not imply superiority of any compound. Head-to-head trials comparing deutetrabenazine or tetrabenazine to valbenazine have not been conducted.”]

>>When all you want is VMAT2 inhibition…

[A large group of arrows representing INGREZZA fly across the screen.]

>>…all you need is INGREZZA.

[INGREZZA arrows all hit the VMAT2 target bullseye.]

>>Only INGREZZA is uniquely selective for VMAT2.

>>[“INGREZZA” jingle]

[The INGREZZA logo is centered on screen.]

>>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 AND 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, at INGREZZAHCP.com.

[Blue gradient builds into screen with logos, references, and codeline.]

[On-screen text reads, “REFERENCES: 1. Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. J Pharmacol Exp Ther. 2017;361(3):454-461. 2. Brar S, Vijan A, Scott FL, et al. Pharmacokinetic and pharmacologic characterization of the dihydrotetrabenazine isomers of deutetrabenazine and valbenazine [published online ahead of print, 2022 Dec 18]. Clin Pharmacol Drug Dev. 2022;10.1002/cpdd.1205. 3. Skor H, Smith EB, Loewen G, O’Brien CF, Grigoriadis DE, Bozigian H. Differences in dihydrotetrabenazine isomer concentrations following administration of tetrabenazine and valbenazine. Drugs R D. 2017;17(3):449-459. 4. Data on file. Neurocrine Biosciences, Inc.”]

©2024 Neurocrine Biosciences, Inc. All Rights Reserved. EP-VBZ-US-0039 09/2024

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