How effective is Ingrezza?

Official answer

by Drugs.com

The effectiveness of Ingrezza improves with time, with maximal effectiveness reported at around 32 weeks for Tardive dyskinesia (TD), and after about 12 weeks for chorea associated with Huntington's disease (HD)..

Effectiveness for TD is usually determined by a significant change from baseline in either the Abnormal Involuntary Movement Scale (AIMS) or the Clinical Global Impression–Tardive Dyskinesia (CGI-TD) scale.

For chorea associated with HD, effectiveness is determined by the least squares mean (LSM) change in chorea severity using the Total Maximal Chorea (TMC) score of the Unified Huntington's Disease Rating Scale (UHDRS).

Trials consistently report over 61% of participants as “much improved” or “very much improved” after 4 to 6 weeks treatment with Ingrezza 50mg to 80mg according to their CGI-TD score. Changes in baseline with AIMS range from -2.4 to -5.8.

Trials for chorea associated with HD reported a 4.6-point improvement in chorea severity score with Ingrezza compared with a 1.4-point improvement with placebo by the end of 12 weeks (mean difference –3.2, 95% CI, –4.4 to –2.0; P < 0.0001). 53% of patients and 43% of health professionals reported that overall, HD chorea symptoms were "very much improved" or "much improved" at Week 12.

Symptoms of tardive dyskinesia return within four weeks of discontinuing Ingrezza.

Symptoms of chorea returned within 2 weeks of discontinuing Ingrezza.

Ingrezza (valbenazine) is an oral medication that may be used to treat symptoms of tardive dyskinesia (TD) in adults. It may also be used to treat adults with chorea associated with Huntington’s disease (HD), a hereditary progressive neurodegenerative disorder. Ingrezza will not cure TD or HD.

Ingrezza belongs to a class of medicines called vesicular monoamine transporter 2 (VMAT2) inhibitors.

How effective is Ingrezza for Tardive dyskinesia (TD)?

Some improvement in TD symptoms may be noticed in as little as 2 weeks; however, it usually takes at least 6 to 8 weeks for significant effects to be seen. Maximal benefits were experienced 32 weeks into treatment. Symptoms of TD returned to baseline levels within four weeks of discontinuing Ingrezza.

Results from trials investigating the effectiveness of Ingrezza (valbenazine) using either tools such as the Abnormal Involuntary Movement Scale (AIMS) or the Clinical Global Impression–Tardive Dyskinesia (CGI-TD) scale were:

KINECT study: Although the change in symptoms from baseline with valbenazine was not significantly different than placebo after 4 weeks of treatment, 61% of participants who continued with valbenazine 50mg were assessed to be “much improved” or “very much improved” according to their CGI-TD score (-5.8 change from baseline with AIMS)

KINECT 2 study: 67% of patients were assessed as very much improved or much improved according to CGI-TD score after 6 weeks of treatment with valbenazine (25mg to 75mg). The AIMS change from baseline was statistically significant at -2.4

KINECT 3 study: Participants received either a placebo, valbenazine 40mg daily, or valbenazine 80mg daily for six weeks. Although symptoms of TD were reduced in both treatment groups, only the 80mg treatment group was statistically significant (change in AIMS scores of valbenazine vs. placebo: -3.2 vs. -0.1). There were no statistically significant differences among groups according to the CGI-TD score. Those who continued treatment for a further 42 weeks reported statistically significant reductions in their mean AIMS score (-3.0 in the 40mg group and -4.8 in the 80mg group) as well as reductions in the CGI-TD.

The most common adverse events of Ingrezza were fatigue, sleepiness, constipation, dry mouth, headache, nausea, and vomiting.

How effective is Ingrezza for chorea associated with Huntington’s disease (HD)?

Some improvement in chorea symptoms have been noticed within 2 weeks of starting a 40mg dose of Ingrezza, and clinically meaningful improvements are noticed with each week of dosing. It may take up to 12 weeks for the full effects to be seen.

In a study that spanned 12 weeks, Ingrezza demonstrated a three-times greater improvement in chorea severity compared with a placebo (an inactive pill). There was a 4.6-point improvement in chorea severity score with Ingrezza compared with a 1.4-point improvement with placebo by the end of 12 weeks (mean difference –3.2, 95% CI, –4.4 to –2.0; P < 0.0001).

The dosage in clinical trials was started at 40mg/day and increased every 2 weeks in 20mg increments, up to a maximum of 80mg/day if needed.

Nearly half of all patients saw a greater than 40% reduction in their chorea symptoms.

53% of patients and 43% of health professionals reported that overall, HD chorea symptoms were "very much improved" or "much improved" at Week 12.

Two weeks after discontinuing Ingrezza, symptoms of chorea associated with HD returned to baseline (what they were before the medication was started).

Ingrezza was generally well tolerated in people with HD with the most common side effects reported as somnolence/lethargy/sedation, urticaria, rash, and insomnia.

Ingrezza carries a boxed warning for a risk of depression and suicidal thoughts. In a 14-week clinical trial, 4.7% of Ingrezza-treated patients reported depression or depressed mood compared with 1.6% of patients receiving placebo.

How does Ingrezza work?

Experts aren’t sure how Ingrezza works but suspect it blocks a protein transporter called vesicular monoamine transporter 2 (VMAT2), which is responsible for regulating the uptake of monoamine neurotransmitters such as dopamine, noradrenaline, and serotonin from the cytoplasm of the cell into the synaptic vessels.

Synaptic vessels store neurotransmitters for release into the synapse (the space between two nerves). These neurotransmitters have various functions within the body but dopamine in particular plays a role in movement as well as pleasure, motivation, and learning.

Abnormal functioning of dopamine is thought to be a cause of TD and chorea associated with HD. By blocking VMAT2, Ingrezza reduces the uptake of monamines, such as dopamine, causing a decrease in symptoms of TD and chorea.

What is tardive dyskinesia (TD)?

TD is a term used to describe a cluster of abnormal, involuntary movements, especially of the lower face, that develop after exposure to antipsychotics or other medications that block dopamine receptors, such as metoclopramide. The abnormal movements include tongue thrusting, repetitive chewing, jaw swinging, lip-smacking, and/or facial grimacing.

Older-generation (typical) antipsychotic medications, such as haloperidol, trifluoperazine, or fluphenazine are the most common causative agents. The condition may be reversible if recognized in the earliest stages, by stopping the causative agent, but may be permanent.

On occasion, if the anti-psychotics are stopped after the tardive dyskinesia has been present for a long period, the condition may become significantly worse.

What is chorea associated with Huntington's disease (HD)?

Huntington's disease (HD) is an inherited disorder that usually starts in middle age, although rarely, there is a form that occurs in children. The condition causes nerve cells (neurons) in areas of the brain that help control voluntary movement to gradually break down and die. People with HD develop uncontrollable, dance-like movements - these are called chorea - in their fingers, feet, face, or torso. Other symptoms include abnormal body postures and problems with behavior, emotion, thinking, and personality. Symptoms can become more intense when the person is nervous or distracted or as the disease progresses with time.

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