Allergan and Gedeon Richter announced positive topline results for a phase 3 study of cariprazine for the treatment of adults with major depressive episodes associated with bipolar I disorder (bipolar I depression). This is the second positive pivotal trial of cariprazine for this investigational use.

In this study, the primary efficacy objective was met for both Cariprazine 1.5mg and 3mg dose groups (p<0.05). Both showed a significantly greater improvement than placebo for the change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) total score.

"These phase 3 data provide further support for  cariprazine as a potential treatment for adults with bipolar depression, and adds to the growing clinical profile of this compound in mental health disorders," said David Nicholson, Chief Research & Development Officer at Allergan. "Bipolar depression is a serious and impairing condition of bipolar I disorder. At Allergan, we're committed to supporting underserved populations with limited treatment options, and look forward to submitting an sNDA for cariprazine as a treatment option for patients suffering from bipolar I depression."

In this study, cariprazine was generally well tolerated. Sedation, somnolence, dizziness, akathisia and nausea were the most commonly reported adverse events (reported with a frequency of 5% or greater and at least twice that of placebo). In this study, 5.0% of cariprazine treated patients discontinued due to adverse events versus 2.5% of placebo treated patients.

The company plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration in the 2nd half of 2018.

RGH-MD-54 is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, fixed-dose clinical trial in patients with bipolar I depression. A total of 488 patients were randomized in this study aiming to evaluate the efficacy, safety, and tolerability of cariprazine 1.5 mg/day and 3.0 mg/day compared to placebo in patients with bipolar I depression. Subjects underwent a no-drug screening period of approximately 7-14 days, followed by 6 weeks of double-blind treatment and a 1-week, no investigational product safety follow-up period.

VRAYLAR is an oral, once daily atypical antipsychotic approved for the acute treatment of adult patients with manic or mixed episodes associated with bipolar I disorder, with a recommended dose range of 3 to 6 mg/day, and for the treatment of schizophrenia in adults, with a recommended dose range of 1.5 to 6 mg/day.

While the mechanism of action of VRAYLAR in schizophrenia and bipolar I disorder is unknown, the efficacy of VRAYLAR could be mediated through a combination of partial agonist activity at central dopamine D? and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Pharmacodynamic studies with cariprazine have shown that it acts as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors. Cariprazine demonstrated up to ~8-fold greater in vitro affinity for dopamine D3 vs D2 receptors. Cariprazine also acts as an antagonist at serotonin 5-HT2B and 5-HT2A receptors with high and moderate binding affinity, respectively as well as it binds to the histamine H1 receptors. Cariprazine shows lower binding affinity to the serotonin 5-HT2C and α1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors. The clinical significance of these in vitro data is unknown.

VRAYLAR was discovered and co-developed by Gedeon Richter and is licensed, Allergan, in the U.S. and Canada. For more than a decade both companies have conducted  over 20 clinical trials enrolling thousands of patients worldwide to evaluate the  efficacy and safety of cariprazine for patients suffering from a broad range of mental health illnesses.