Brexpiprazole for schizophrenia

Background: Brexpiprazole (proposed proprietary name “Rexulti”) is a new molecular entity atypical antipsychotic co-developed by Otsuka Pharmaceutical Co, Ltd (Otsuka) and H. Lundbeck A/S (Lundbeck). The mechanism of action is unknown.

Methods: The FDA site was searched to locate relevant documents.  If these were not sufficient then EPARs from the European Medicines Agency were to be used.  Relevant data was extracted and used for a meta-analysis via RevMan. No journal articles were used.  The method is a pragmatic rapid systematic review.  The estimated time for the whole process was 60-90 minutes.

Primary efficacy endpoint: Mean reduction in PANSS total score at week 6.

Number of trials: 2. Study 230 = 657 patients, Study 231 = 623 patients.

Results:

The above table is a summary of the 6 week results.  Below is the data presented as a meta-analysis for both doses:

Over 6 weeks 2mg brexpiprazole produced a mean change in PANSS of 5.8, while the 4mg dose produced a change of 7.1.

Adverse events: In short-term, controlled trials, the percentage of subjects reporting >1 treatment-emergent adverse events (TEAEs) was similar in the brexpiprazole 2-4 mg/day, all brexpiprazole, and placebo groups (59.2%, 60.6%, and 61.1% respectively). Events reported by >5% of subjects the all brexpiprazole group included headache, akathisia, insomnia, and agitation. Only akathisia was reported by a higher percentage of subjects in the all brexpiprazole group than in the placebo group, and it did not reach the “most common” threshold of >5% and >2x placebo.

Conclusion: Compared with placebo, brexpiprazole appears to be effective in relation to the short-term (6 week) measure of reduction in PANSS.

References

• FDA Medical Review
• FDA Statistical Review
• Study 230: A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res. 2015 May;164(1-3):127-35
• Study 231: Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial. Am J Psychiatry. 2015 Sep 1;172(9):870-80
• Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015
• Example rapid review: Feedback from Erick Turner