Allergan plc, the world's third-largest global generics business, and Gedeon Richter Plc., a major pharmaceutical company, announced that the US Food and Drug Administration (FDA) has approved Vraylar (cariprazine) capsules, an atypical antipsychotic, for the acute treatment of manic or mixed episodes associated with bipolar I disorder and for treatment of schizophrenia in adults.

"We are pleased with the FDA approval of Vraylar, which represents an important new treatment option for adults living with bipolar I disorder and schizophrenia to help address the unmet medical needs of people with these complex conditions," said David Nicholson, executive vice president and president of global R&D brands of Allergan.

"This approval reinforces our deep commitment to the mental health community, as we continue to build our robust CNS portfolio."

Bipolar I disorder and schizophrenia are chronic and disabling mental health disorders. Bipolar I disorder, also known as manic-depressive illness, is a disorder of the brain that is characterized by fluctuations in mood, energy, activity levels, and the ability to carry out day-to-day tasks. Bipolar disorder affects approximately 3.6 million people in the United States. Schizophrenia is characterized by delusions, hallucinations, disorganised speech and behaviour, and other symptoms that cause social or occupational dysfunction. Schizophrenia is a chronic and disabling disorder that affects more than 2.6 million American adults. It imposes significant burden on patients, their families, and society.

"Bipolar I disorder and schizophrenia are serious, chronic and treatable conditions. The symptoms and response to treatment vary from patient to patient making these conditions challenging to manage," said Gary Sachs, MD, founding director of the Bipolar Clinic and Research Programme at the Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School.

The FDA approval of Vraylar is based on the results of three 3-week controlled trials in adults with manic or mixed episodes of bipolar I disorder and three 6-week placebo-controlled trials in adults with schizophrenia. In these clinical trials involving more than 2,700 adults, Vraylar demonstrated improvement compared to placebo as measured by Young Mania Rating Scale (YMRS) total scores in patients with bipolar mania and by Positive and Negative Syndrome Scale (PANSS) total scores in patients with schizophrenia. Vraylar also demonstrated efficacy as measured by the Clinical Global Impressions-Severity (CGI-S) rating scale, the secondary efficacy endpoints for both conditions.

"This approval is a notable achievement for Gedeon Richter's discovery platform," said Erik Bogsch, managing director of Richter Gedeon Plc.

"Despite the variety of treatments available for the millions living with bipolar I disorder and schizophrenia, unmet needs remain and we are proud to offer an additional option to help patients manage their symptoms."

The most commonly reported adverse reactions (incidence = 5 per cent and at least twice the rate of placebo) in bipolar mania were extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness and in schizophrenia were extrapyramidal symptoms and akathisia.

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. The safety and efficacy of Vraylar was studied in a clinical trial programme of more than 2,700 patients with these conditions.

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 D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors.

Pharmacodynamically, cariprazine acts as a partial agonist at the dopamine D3 and D2 receptors with high binding affinity and at the serotonin 5-HT1A receptors. Cariprazine acts as an antagonist at 5-HT2B and 5-HT2A receptors with high and moderate binding affinity as well as it binds to the histamine H1 receptors. Cariprazine shows lower binding affinity to the serotonin 5-HT2C and a1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors.

Vraylar was discovered and co-developed by Gedeon Richter Plc and is licensed to Actavis, now Allergan, in the US and Canada.

Cariprazine is also being investigated for the treatment of bipolar depression and as adjunctive treatment for major depressive disorder in adults.