Ingrezza (valbenazine) for Huntington’s disease

Last updated Aug. 25, 2023, by Marisa Wexler, MS

✅ Fact-checked by Marta Figueiredo, PhD

What is Ingrezza for Huntington’s disease?

Ingrezza (valbenazine) is an oral medication approved in the U.S. to treat adults with Huntington’s disease who experience the involuntary, jerky movements known as chorea that are a hallmark of the rare disorder.

Developed by Neurocrine Biosciences, the therapy also is approved for adults with tardive dyskinesia, a movement disorder marked by facial tics.

How does Ingrezza work?

Huntington’s is an inherited, progressive neurodegenerative disease characterized by both motor and nonmotor symptoms. The most notable motor sign is chorea, which affects about 90% of Huntington’s patients and is known by its involuntary and uncontrollable movements.

Chorea can affect several parts of the body and negatively impact motor coordination, walking ability, and posture, as well as swallowing and speech.

Huntington’s-associated chorea is thought to be associated with unusually high levels in the body of dopamine, a major brain chemical messenger, or neurotransmitter, that plays key roles in coordinating movement.

Ingrezza is a small molecule that potently and selectively blocks the activity of a protein called vesicular monoamine transporter 2, or VMAT2. This protein is responsible for neurotransmitter transport and recycling at the synapse, the point of near contact between nerve cells where they release molecules to communicate with each other.

While Ingrezza’s precise mechanism of action isn’t fully understood, its ability to suppress VMAT2 is thought to reduce the amount of dopamine that’s released by nerve cells at the synapse. That, in turn, is believed to dial back activation of neighboring nerve cells. By lowering dopamine signaling in the brain, the therapy is expected to reduce chorea among patients.

Who can take Ingrezza?

Ingrezza was approved by the U.S. Food and Drug Administration (FDA) in August 2023 to treat adults with chorea associated with Huntington’s.

The decision made Ingrezza the first approved VMAT2 suppressor to offer an effective starting dosage that can be adjusted based on response and tolerability, with no complex dose-optimization, according to Neurocrine.

The medication is not yet approved in any other countries for Huntington’s-associated chorea.

Who should not take Ingrezza?

Ingrezza is not recommended for patients with a known allergy to valbenazine or any other ingredient in the medication.

The medication also carries a boxed warning noting it may increase the risk of depression and suicidal thoughts in people with Huntington’s, so caution is recommended when treating individuals with a history of depression or those who have had suicidal thoughts or suicide attempts in the past.

The therapy should not be taken in combination with medications that are strong CYP3A4 inducers, such as the antibiotic rifampicin. CYP3A4 is a liver enzyme that’s key for the metabolism of many medications.

Patients on monoamine oxidase (MAO) inhibitors, a type of antidepressive medication, also should avoid taking Ingrezza simultaneously and during the first two weeks after discontinuation of the MAO inhibitor treatment.

Ingrezza also should be avoided in patients who have certain types of abnormal heart rhythms.

How is Ingrezza administered in Huntington’s disease?

Ingrezza is available in the form of oral capsules that exist in three dosage strengths:

  • 40 mg capsules, which have a white opaque body and purple cap, both printed with “VBZ” and “40” in black ink
  • 60 mg capsules, with a dark red opaque body and purple cap, both printed with “VBZ” and “60” in black ink
  • 80 mg capsules, which have a purple opaque body and cap, and are printed with “VBZ” and “80” in black ink.

The recommended starting daily dose of Ingrezza is 40 mg, or one 40 mg capsule per day, taken by mouth. After two weeks, the dose can be upped to 60 mg/day, and then after another two weeks, it can be increased to the recommended maintenance dose of 80 mg once daily.

Lower maintenance doses — specifically of 40 or 60 mg/day — may be considered based on a patient’s response to treatment and ability to tolerate the medication.

The dosage also should be reduced to 40 mg per day in patients who:

  • have moderately to severely impaired liver function
  • are known to have poor activity of CYP2D6, another liver enzyme that’s involved in the metabolism of several medications
  • are taking medications that are strong suppressors of CYP3A4 or CYP2D6.

Ingrezza can be taken with or without food.

Ingrezza in clinical trials

The FDA’s approval of Ingrezza for Huntington’s-associated chorea was based mainly on data from a Phase 3 clinical trial called KINECT-HD (NCT04102579), completed in October 2021.


The KINECT-HD study enrolled 128 adults with chorea related to Huntington’s at 46 sites across North America. Participants were given an oral capsule of either Ingrezza or a placebo, once daily for 12 weeks, or about three months. The therapy was started at a daily dose of 40 mg and gradually increased to 80 mg/day based on tolerability.

The trial’s main goal was to evaluate changes in chorea severity, as assessed with the Total Maximal Chorea score of the Unified Huntington’s Disease Rating Scale (UHDRS). This measure evaluates chorea in the face, mouth/jaw, trunk, and each limb, with higher scores indicating worse chorea.

The results showed that, on average, chorea scores dropped by 4.6 points in Ingrezza-treated patients and by 1.4 points in those given the placebo — a more than three-point difference that was statistically significant. After three months, nearly half of patients on Ingrezza had experienced a reduction in chorea severity of more than 40%.

Reductions in chorea scores were seen as early as two weeks after patients started on Ingrezza. Also, considerable improvements in overall health were significantly more common in the Ingrezza group than among those on the placebo, as reported both by patients (43% vs. 13%) and by clinicians (53% vs. 26%).

KINECT-HD was the first Phase 3 trial to use a new validated measure of patient-reported disease burden in Huntington’s. This measure is called the Huntington’s Disease Health Index, or HD-HI. Results using this assessment confirmed Ingrezza’s superiority over the placebo, with the medication leading to a greater reduction in disease burden associated with uncontrolled movements, mobility problems, and hand and arm dysfunction.

Ongoing trials

An open-label extension study called KINECT-HD2 trial (NCT04400331) is evaluating the long-term safety and efficacy of Ingrezza in adults who have chorea due to Huntington’s.

The trial was open both to patients who completed the KINECT-HD study and to other adults with Huntington’s-associated chorea. All participants are receiving the therapy for up to three years.

Common side effects of Ingrezza

The most common side effects of Ingrezza in people with Huntington’s include:

  • sleepiness, lethargy, or sedation
  • hives (urticaria)
  • rash
  • insomnia.

Depression and suicidal ideation

Ingrezza carries a boxed warning noting that it may increase the risk of depression and suicidal thoughts or behaviors in people with Huntington’s, who already are at risk of these problems.

Before starting Ingrezza, patients and their healthcare team should discuss whether the need for treatment outweighs the risk of depression and suicidal thoughts or actions.

Those starting on the therapy or who change their dose should be closely monitored for new or worsening signs of these issues, and patients, caregivers, and family members should be aware of this risk and report sudden changes in mood, behaviors, thoughts, or feelings to the treating physician.

If patients show new or worsening signs of depression, suicidal thoughts and/or behaviors that do not resolve, Ingrezza discontinuation should be considered.

Allergic reactions

Ingrezza may cause allergic reactions, including rash, hives, and tissue swelling that can be life-threatening if it affects the throat and blocks the airways. Ingrezza treatment should be stopped if an allergic reaction occurs, and patients should seek immediate medical care if they experience any swelling symptoms.

Drowsiness and sedation

Sleepiness, also known as somnolence, and sedation were the most commonly reported side effects of Ingrezza in clinical trials. It is recommended that people starting on Ingrezza avoid driving, operating heavy machinery, or doing other activities that require alertness until they know how the medication affects them.

Abnormal heart rhythms

Ingrezza can cause a change in heart rhythm known as QT prolongation. These changes are not usually clinically significant at the therapy’s recommended dose, but may become so in people taking strong CYP2D6 or CYP3A4 inhibitors, or in those with poor CYP2D6 activity.

The therapy should not be given to patients with a syndrome associated with QT prolongation or with heart rate abnormalities characterized by QT prolongation. For patients at increased risk of these abnormalities, their heart rhythm should be assessed prior to starting on Ingrezza or increasing their daily dosage.

Neuroleptic Malignant Syndrome, or NMS

Ingrezza and other therapies that work by blocking VMAT2 can cause a life-threatening neurological disorder called neuroleptic malignant syndrome, or NMS, which is marked by high fever, rigid muscles, an altered mental state, and heart rhythm and blood pressure abnormalities.

If NMS occurs, Ingrezza should be discontinued immediately, and patients should be given intensive medical care to manage any symptoms. In case where Ingrezza is restarted, patients should be monitored for signs of NMS recurrence.

Parkinson’s-like symptoms

Ingrezza may cause symptoms similar to those seen in Parkinson’s disease, known as parkinsonism. These symptoms include slowed movement (bradykinesia), tremor, rigidity, and problems with balance.

If patients develop clinically significant parkinsonism while on Ingrezza, the dose should be reduced or the treatment should be stopped.

Use in pregnancy and breastfeeding

There is not enough data available to make robust conclusions about the safety of Ingrezza when used in patients who are pregnant or breastfeeding. However, animal data suggest that the medication may harm a developing fetus and/or nursing infant, as administering the therapy to rats from pregnancy through lactation led to an increase in the number of stillborn pups.

Patients who are pregnant or plan to become pregnant should discuss this topic with their healthcare team and carefully weigh the potential benefits and risks of using Ingrezza in these circumstances.

The therapy’s presence in human breast milk and its potential effects on a breastfed infant or on milk production in nursing patients remain unknown. Still, patients are advised not to breastfeed while taking the medication and for at least five days after stopping Ingrezza treatment.

Huntington’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.