FDA Considers Labeling Update for Schizophrenia Drug Brexpiprazole (Rexulta)

Application seeks approval for maintenance treatment of adults with schizophrenia

The FDA has accepted for review a supplemental new drug application (sNDA) for a proposed labeling update of brexpiprazole (Rexulta, Otsuka/Lundbeck) for the maintenance treatment of adults with schizophrenia. The Prescription Drug User Fee Act (PDUFA) date is September 23, 2016.

The sNDA was supported by results from a 52-week randomized withdrawal trial in adults (18 to 65 years of age) with schizophrenia. Patients were stabilized on brexpiprazole and were then randomly assigned to continue therapy with brexpiprazole (n = 96) or placebo (n = 104). The study’s primary endpoint was the time from randomization to relapse. In a prespecified interim analysis, the study demonstrated a significantly longer time to relapse in the brexpiprazole group (1 to 4 mg/day) compared with the placebo group. The trial was terminated early because maintenance of efficacy had been demonstrated (P < 0.0001, final analysis).

The mechanism of action of brexpiprazole in the adjunctive treatment of major depressive disorder or schizophrenia is not known. However, the drug’s efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. Brexpiprazole exhibits high affinity (subnanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors. The drug was approved in the U.S. on July 10, 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder and as a treatment in adults with schizophrenia.

Source: Lundbeck; February 8, 2016.