Ingrezza Gains Approval for Huntington Disease Chorea

The Food and Drug Administration (FDA) has approved Ingrezza^® (valbenazine) for the treatment of adults with chorea associated with Huntington disease.

Ingrezza is an inhibitor of vesicular monoamine transporter 2 (VMAT2), a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release. The approval was based on data from the double-blind, placebo-controlled KINECT-HD study (ClinicalTrials.gov Identifier: NCT04102579), which included adults diagnosed with chorea associated with Huntington disease.

Patients were randomly assigned to receive valbenazine orally once daily (started at 40mg/day and increased every 2 weeks in 20mg increments up to a max of 80mg/day if needed) or placebo for 12 weeks. The primary endpoint was the change in the Unified Huntington Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score from baseline to the end of the treatment period (average score at weeks 10 and 12). The TMC score is rated from 0 (no chorea) to 4 for 7 different parts of the body; total scores range from 0 to 28.

The efficacy analysis included 125 patients (mean age, 54 years); 46% were male and 96% were White. At the end of the treatment period more than 80% of patients were taking the 80mg daily dosage.

Findings showed that among patients receiving valbenazine, the mean reduction (improvement) in TMC was 4.6 units compared with 1.4 units in the placebo group (least squares mean difference, -3.2 (95% CI, -4.4, -2.0); P <.0001). Two weeks after discontinuing the study medication, the TMC scores for patients who received valbenazine returned to baseline.

Treatment with valbenazine was also associated with statistically significant improvements in overall Huntington chorea symptoms based on clinician-rated global impression of change response status (“much improved” or “very much improved”: 43% with valbenazine vs 13% with placebo; P <.001) and patient-rated global impression of change response status (“much improved” or “very much improved”: 53% with valbenazine vs 26% with placebo; P <.01) at week 12.

“Clinical results that led to this important approval showed reduction in the severity of chorea as early as 2 weeks after starting Ingrezza at an initial dose of 40mg, with consistently greater improvements vs placebo seen at all subsequent visits,” said Erin Furr Stimming, MD, FAAN, FANA, Principal Investigator, Huntington Study Group and Professor of Neurology, McGovern Medical, UTHealth Houston. “Data also demonstrated Ingrezza was generally well tolerated and showed clinically meaningful improvement in adults with chorea associated with HD.”

The most common adverse reactions reported were somnolence/lethargy/sedation, urticaria, rash, and insomnia. The prescribing information for Ingrezza includes a Boxed Warning regarding the risk of depression and suicidal thoughts and behavior in patients with Huntington disease; treatment with VMAT2 inhibitors may increase this risk. In the 14-week clinical trial, 4.7% of Ingrezza-treated patients reported depression or depressed mood compared with 1.6% of patients receiving placebo. Suicidal ideation or behavior was reported in 1 patient receiving placebo and none of the patients receiving Ingrezza.

Ingrezza is supplied as a capsule in 40mg, 60mg, and 80mg dosage strengths. To help patients gain access to treatment, Neurocrine Biosciences has established the INBRACE^® Support Program.

Ingrezza is also indicated for the treatment of tardive dyskinesia.