Brexpiprazole Phase 3 Trials Initiated for Bipolar Treatment

Otsuka Pharmaceutical Co., and Lundbeck announced patient enrollment in 2 phase 3 global clinical trials evaluating brexpiprazole for the treatment of patients with manic episodes associated with bipolar I disorder.

The trials are to evaluate the efficacy of brexpiprazole in patients with bipolar I disorder who experience an acute manic episode with or without mixed features, requiring hospitalization. Mixed features indicate that at least 3 symptoms of depression must accompany the episode.

"Bipolar I disorder is a highly recurrent and chronic mental illness," Ruth Duffy, PhD, Medical Director for Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., told MD Magazine. "As with any neuropsychiatric condition, it can be challenging to treat, which is why we are interested in studying the efficacy and safety of brexipiprazole in this patient population. We are committed to helping patients reach their treatment goals through developing and delivering medicines targeting neuropsychiatric disorders.”

The primary endpoint of the double-blind, randomized trials is the mean change from baseline to day 21 in the Young-Mania Rating Scale (YMRS) total score. The score is a widely used clinician rating scale that assess mania symptoms based on a patient’s subjective reports of their condition and clinical observations made during interviews.

Key secondary endpoints include the change from baseline to day 21 in Clinical Global Impression — Bipolar (CGI BP) severity-of-illness score in mania, as well as monitoring of the safety and tolerability.

While the mechanism of action is unknown, the efficacy of brexpiprazole 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. It exhibits high affinity for these receptors, along with noradrenaline alpha 1B/2C receptors.

In July 2015, brexpiprazole was approved by the US Food and Drug Administration for treatment of patients with schizophrenia, and as an adjunctive treatment for patients with Major Depressive Disorder (MDD). This year, Health Canada approved brexpiprazole for schizophrenia in February, while the Australian Department of Health granted approval for the same indication in May.

In an exclusive interview with MD Magazine, Duffy discusses a study conducted on patients with schizophrenia who responded well in the acute study to brexpiprazole, and then moved over to a long-term maintenance study. The safety study focused on the length of remission and found that over a year of treatment, close to 35% of patients who started out acutely ill, met the criteria for sustained remission past at least 6 months while using brexpiprazole.

“There’s always a need to provide patients with another option that may help them maintain their symptomology and keep it under control, and also help them move forward in their lives and potentially have a sustained response over time that may help improve their long-term outcomes,” Duffy said. “Brexpiprazole provides that option for those patients.”

This year, Health Canada approved brexpiprazole for schizophrenia in February, while the Australian Department of Health granted approval for the same indication in May.

Brexpiprazole is currently distributed and marketed under the brand name Rexulti in the US, Canada and Australia.

A press release was made available.