REXULTI Rx

The approval was based on data from two 12-week, double-blind, placebo-controlled phase 3 studies (Study 331-12-283 and Study 331-14-213) in which patients with dementia due to Alzheimer disease were randomly assigned to receive either brexpiprazole or placebo.

Study participants were required to have a diagnosis of probable Alzheimer disease (according to NINCDS-ADRDA criteria), have a Mini-Mental State Examination score of at least 5 and less than or equal to 22 and have a total score of at least 4 by the agitation/aggression item of the NPI/NPI-NH, and exhibit sufficient agitation behaviors at time of entry to warrant use of pharmacotherapy, after excluding other factors.

The primary endpoint for both studies was the change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score at week 12. The CMAI consists of 29 items that assess the frequency and manifestations of agitated behaviors in elderly patients, based on caregiver input. Total scores range from 29 (best) to 203 (worst).

In Study 331-12-283, results showed that treatment with brexpiprazole 2mg/day significantly improved symptoms of agitation compared with placebo based on the mean change in CMAI total score from baseline to week 12 (placebo-subtracted difference: -3.8 [95% CI, -7.4, -0.2]; P <.05). A statistically significant improvement was also observed with brexpiprazole 2mg/day and 3mg/day compared with placebo in Study 331-14-213 (placebo-subtracted difference: -5.3 [95% CI, -8.8, -1.9]; P <.05).

Rexulti was studied in two 6-week, placebo-controlled clinical trials of adults with MDD. Study participants met DSM-IV-TR criteria for MDD and had an inadequate response to prior antidepressant therapy (ADT; 1 to 3 courses) in the current episode and also demonstrated an inadequate response throughout the 8 weeks of prospective antidepressant treatment.

The primary endpoint for both studies was change in Montgomery-Åsberg Depression Rating Scale (MADRS). Study data showed that Rexulti plus ADT at 2mg and 3mg was superior to placebo. A decrease in baseline MADRS of 8.4 (2mg) and 8.3 (3mg) was seen vs placebo + ADT decreases of 5.2 and 6.3 in the respective studies.

Rexulti was studied in two 6-week, phase 3 randomized, placebo-controlled trials in adults with schizophrenia comparing fixed doses of Rexulti vs placebo. Study data showed treatment with Rexulti for 6 weeks showed statistically significant efficacy for the primary endpoint of Positive and Negative Syndrome Scale (PANSS). In one trial, the change from baseline in PANSS total score in the Rexulti group was -20.7 (2mg) and -19.7 (4mg) vs -12.0 in the placebo group. In the second trial, the change from baseline in PANSS total score was -20.0 in the Rexulti 4mg group vs -13.5 in the placebo group; the 2mg dose was not superior to placebo in this trial.

Maintenance treatment for schizophrenia was evaluated in a long-term randomized withdrawal trial in adults aged 18–65 years. After patients were cross-titrated from a prior antipsychotic to Rexulti and underwent a 12-36 week single-blind Rexulti stabilization phase, those who were symptomatically stable on Rexulti for 12 consecutive weeks in the stabilization phase were then randomized in a double-blind treatment phase to either Rexulti (n=97) or placebo (n=105). 

Relapse during the double-blind phase was established if patients met any of the following criteria: worsening symptoms defined by changes in PANSS or CGI-I scores; hospitalization for worsening psychotic symptoms; suicidal behavior, or violent/aggressive behavior. 

An interim analysis showed a statistically significant longer time to relapse in patients who took Rexulti vs placebo. This trial was terminated early because maintenance of efficacy was demonstrated. The final analysis showed a statistically significant longer time to relapse (hazard ratio [HR] 0.292; P <.0001) in patients who took Rexulti vs placebo. In addition, the proportion of patients who met the criteria for impending relapse (secondary endpoint), was statistically significantly lower in Rexulti-treated patients vs placebo group.