Allergan to File for Approval of Bipolar I Depression Drug After Late-Stage Trial Success

Allergan has reported another win for its bipolar I depression drug cariprazine in its third Phase III clinical trial. While the drug is currently sold in the US under the name Vraylar as a treatment for schizophrenia and manic episodes associated with bipolar I disorder, Allergan and its development partner Gedeon Richter Plc. are hoping to grab another indication for the antipsychotic drug.

In late 2017, the companies released positive results for their second Phase III trial which found that both doses of cariprazine beat the placebo on the Montgomery-Asberg Depression Rating Scale (MADRS), a measure of the severity of depressive episodes. In the current study, only the 1.5 mg dose of the drug was found to show a statistically significant improvement over the placebo after six weeks of treatment on the MADRS and the Clinical Global Impression Scale-Severity (CGI-S).

“We are very pleased with the results of our third pivotal study, which reinforce the wealth of data supporting cariprazine as a potential treatment in adults with bipolar depression,” said David Nicholson, Chief Research & Development Officer at Allergan. “Bipolar depression is often difficult to treat and can be extremely debilitating for patients. At Allergan, we are committed to developing treatments that address unmet needs facing people living with mental illness and are looking forward to submitting an sNDA for cariprazine for patients suffering with bipolar I depression.”

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Allergan’s most recent Phase III clinical trial of cariprazine involved nearly 500 patients diagnosed with bipolar I depression who were randomly assigned to receive the drug at a dose of 1.5 mg or 3 mg, or the placebo. The company plans to include data from all three late-stage trials in a Supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) to be submitted later this year.

Despite its apparent efficacy in treating depressive symptoms of bipolar I disorder, the mechanism of action of cariprazine is unknown. According to Allergan, Vraylar could have “partial agonist activity at central dopamine D₂ and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors” however this proposed mechanism of action is largely based on in vitro data which may, or may not, be clinically significant.

“Treating bipolar depression can be very difficult given the few therapies available to manage these symptoms of bipolar I disorder. Further, there are a limited number of products available to help treat the full range of bipolar disorder – from mania through depression,” said Dr. Gary Sachs, Associate Clinical Professor of Psychiatry at Harvard Medical School. “This data is encouraging for patients and the broader psychiatry community, as it demonstrates cariprazine’s potential in treating the full spectrum of the disorder.”