Regulatory Decision Summary for Abilify Maintena

Abilify Maintena is a long-acting injectable antipsychotic agent currently approved in Canada for the maintenance treatment of schizophrenia. The current application to extend the indication of Abilify Maintena to include the treatment of acute episodes of schizophrenia is supported by one short-term (12 weeks), multicentre, randomized, double-blind, and placebo-controlled pivotal trial of Abilify Maintena in acutely ill patients with schizophrenia.

In the pivotal trial, patients received either aripiprazole [intramuscular (IM)] depot 400 mg/300 mg or matching placebo injected into a gluteal muscle every 4 weeks [that is (i.e.), baseline/Day 0, Week 4, and Week 8] during the 12-week Acute Treatment Phase for a total of three IM depot injections. For the first 14 days, patients randomized to aripiprazole IM depot received concomitant oral aripiprazole and patients randomized to placebo received concomitant oral placebo (as per the standard currently approved Product Monograph dosing recommendations). Even though this was a 12-week, randomized, double‑blind trial, the primary efficacy endpoint was the change from baseline to Week 10 in Positive and Negative Syndrome Scale (PANSS) total score, and the raters were blind to the primary endpoint.

The study population was acutely ill as indicated by the magnitude of baseline PANSS and Clinical Global Impression Severity Scale (CGI-S) scores. Abilify Maintena was superior to placebo on the primary outcome measure (change from baseline in PANSS total score at Week 10), supporting the use of Abilify Maintena in treating an acute psychotic episode of schizophrenia. There was one confounding factor in that oral Abilify (or matching placebo) was used for the first 2 weeks of the trial (following the first injection). This is the standard dosing procedure for Abilify Maintena, as it takes Abilify Maintena up to 2 weeks to reach therapeutic plasma levels. This dosing procedure makes it impossible to separate the effects of oral Abilify from the effect of the Abilify Maintena injection for the first few weeks of the trial. Nevertheless, the differences in the Abilify Maintena group compared to the placebo group (in PANSS total score change from baseline) continued to increase up to the primary efficacy outcome assessment endpoint of 10 weeks, thereby supporting the efficacy of the injection.

Safety data for the use of Abilify Maintena for the treatment of acute episodes of schizophrenia were primarily obtained from the trial above. In addition, the sponsor provided safety data from a 26-week open-label extension of the acute trial. A Periodic Benefit-Risk Evaluation Report was also provided covering the period of July 17, 2013 through July 16, 2014. No new safety issues were identified in the current submission. The safety profile of Abilify Maintena in treatment of acute episodes of schizophrenia was similar to that previously observed in maintenance treatment.

Given the previously established efficacy of Abilify oral tablets in acute and maintenance treatment of schizophrenia, and the previously established efficacy of Abilify Maintena in maintenance treatment of schizophrenia, the results of one positive pivotal trial of Abilify Maintena for the treatment of acute episodes of schizophrenia was considered sufficient to support efficacy. The submitted trial supports acute efficacy of Abilify Maintena with a safety profile not dissimilar from its use in maintenance treatment. The risk/benefit profile is deemed acceptable for the extended indication.