Regulatory Decision Summary for Abilify Maintena

Poor adherence to medications for bipolar I disorder significantly adversely affects the course of the disease and is a frequent cause of relapse and recurrence and increased hospitalization and suicide rates. Although oral formulations of atypical antipsychotics have demonstrated positive benefit-risk profiles in patients with bipolar I disorder, long-acting injectable formulations of atypical antipsychotics provide assured delivery and more consistent plasma levels of medication. They also have documented positive impact on treatment adherence and thus may improve patient outcomes.

Currently available mood stabilizers and anticonvulsants used as first-line therapy for acute and maintenance treatment of patients with bipolar I disorder, are limited by their adverse event profiles and the requirement for regular monitoring to maintain therapeutic plasma levels.

Abilify tablets are already approved for the treatment of bipolar I disorder, either as monotherapy or as co-therapy with lithium or divalproex sodium. The purpose of this submission was to assess the efficacy of Abilify Maintaina monthly injections for the treatment of bipolar I disorder.

The results of the trial revealed that the efficacy of Abilify Maintena in bipolar I disorder was superior to placebo, and similar to other products approved for the same indication. The relapse rate in double-blind controlled studies at 52 weeks for Abilify Maintena was 26.5% (vs 51.1% Placebo). In general, the incidence of adverse events (AEs) was low and fairly comparable between Abilify Maintena and other products, with the exception of placebo subtracted akathisia which was higher with Abilify (11% in Abilify Maintena and <2% in Risperdal Consta). However, placebo subtracted incidence of akathisia for Abilify Maintena (11%) is similar to that for Abilify Tablets (9%), therefore this adverse event is already known for Abilify.

Data presented in this submission demonstrate that once-monthly injections of aripiprazole intramuscular (IM) depot are efficacious for maintenance monotherapy treatment in subjects with bipolar I disorder with a known safety profile. Treatment with aripiprazole IM depot reduced the time to and risk of recurrence of mood episodes over 52 weeks, and also delayed the time to and risk of hospitalization due to recurrence of any mood episode over the same time period. In addition, the findings from both Trial 31-08-250 and Trial 31-08-252 did not result in the identification of any new safety signals, further supporting the well-known safety and tolerability profile of aripiprazole oral and IM depot.

In conclusion, the benefit-risk profile of aripiprazole IM depot for maintenance monotherapy treatment of bipolar I disorder is favorable and a Notice of Compliance was issued.