Ingrezza Shows Promise in Late-Stage Dyskinesia Trial

FDA approval decision expected in April

Positive results have been reported from a phase 3 study of valbenazine (Ingrezza, Neurocrine Biosciences), a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, for the treatment of patients with tardive dyskinesia. Once-daily valbenazine demonstrated a significant reduction in TD symptoms compared with placebo in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. The findings were published online in the American Journal of Psychiatry.

Neurocrine Biosciences has submitted a new drug application to the FDA for valbenazine and has been granted a priority review, with a Prescription Drug User Fee Act (PDUFA) action date of April 11, 2017. Neurocrine also received a breakthrough therapy designation from the FDA in 2014 for valbenazine for the treatment of patients with TD.

The Kinect 3 trial was a randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in which 234 subjects with TD and underlying schizophrenia, schizoaffective disorder, or mood disorder (including bipolar disorder or major depressive disorder) received six weeks of once-daily valbenazine (40-mg or 80-mg capsules) or placebo. After this period of placebo-controlled dosing, all of the subjects received once-daily doses of valbenazine (40 mg or 80 mg) through week 48.

The study met its primary endpoint of a change from baseline in the Abnormal Involuntary Movement Scale (AIMS) at week 6 in the 80-mg valbenazine group compared with the placebo group. The mean change from baseline to week 6 in the AIMS score was –3.2 for 80-mg valbenazine compared with –0.1 for placebo (P < 0.0001).

In addition, the percentage of participants who achieved an AIMS response (defined as a reduction of 50% or greater from baseline in the AIMS dyskinesia score) was higher in the 80-mg valbenazine group compared with the placebo group at all study visits. At week 6, 40.0% of participants receiving 80-mg valbenazine had at least a 50% improvement in the AIMS dyskinesia score compared with 8.7% of the placebo group (P < 0.001).

TD is believed to affect at least 500,000 people in the United States and is characterized by uncontrollable, abnormal, repetitive movements of the trunk, extremities, and/or face. These symptoms are associated with chronic exposure to dopamine receptor blockers, such as antipsychotic medications, and can be severe, persistent, and irreversible. In some cases, they can even interfere with speech, walking, swallowing, and breathing.

Source: Neurocrine Biosciences; March 21, 2017.