Vraylar (cariprazine) for the Treatment of Bipolar Disorder and Schizophrenia, United States of America
Vraylar (cariprazine) is a once-daily, oral, atypical antipsychotic drug indicated for the treatment of adults with bipolar I disorder and schizophrenia. The drug was discovered and co-developed by Gedeon Richter and is licenced to Allergan in the US and Canada.
Discovered and developed by Alkermes, Aristada is an antipsychotic drug indicated for the treatment of schizophrenia in adults.
The drug was approved by the US Food and Drug Administration (FDA) in September 2015 for the acute treatment of manic or mixed episodes associated with bipolar I disorder and schizophrenia. The approval followed the resubmission of new drug application (NDA) for the drug in January 2015.
Vraylar is also being investigated for the treatment of bipolar depression and as an adjunctive treatment for major depressive disorder in adults.
Bipolar I disorder and schizophrenia
Bipolar I disorder and schizophrenia are chronic mental health disorders. Patients with bipolar I disorder often experience mood swings, fluctuations in energy and activity levels, and difficulty in conducting day-to-day tasks. It affects approximately 3.6 million people in the US.
Schizophrenia is associated with hallucinations, speech difficulties and poor social behaviour. Symptoms of the disorder broadly fall under three categories, namely positive, negative and cognitive. An estimated 2.6 million adults suffer from schizophrenia in the US.
Vraylar's mechanism and action and dosage
hough Vraylar's mechanism of action in treating bipolar I disorder and schizophrenia is not clearly known, its efficacy could be linked to the combination of partial agonist activity and antagonist activity exhibited at the central dopamine D2 and serotonin 5-HT1A 5-HT2A receptors.
While cariprazine acts as a partial agonist at the dopamine D3 and D2 receptors, it acts as an antagonist at serotonin 5-HT2B and 5-HT2A receptors.
The recommended dose range of the drug for adult patients with manic or mixed episodes associated with bipolar I disorder is between 3mg/day and 6mg/day, while it is between 1.5mg/day to 6mg/day for schizophrenia patients.
Clinical trials on Vraylar
The FDA approval for Vraylar is based on the results from a clinical trial programme conducted to establish the safety and efficacy of the drug in patients with manic or mixed episodes of bipolar I disorder and schizophrenia.
The drug's efficacy in the treatment of schizophrenia was established in three six-week, randomised, double-blind and placebo-controlled trials. The primary and secondary efficacy measures to assess psychiatric signs and symptoms in each trial were determined using the positive and negative syndrome scale (PANSS) and Clinical Global Impressions-Severity (CGI-S) rating scales. The primary endpoint in each study was change from baseline in PANSS total score at the end of week six.
Study 1 was a placebo-controlled study, which enrolled 711 patients, and involved three fixed doses of Vraylar and an active control (risperidone). All the drug doses, including the active control, demonstrated superior results compared to placebo on the PANSS total score and the CGI-S.
Study 2 enrolled 604 patients and involved two fixed doses of Vraylar and an active control (aripiprazole), all of which were proved to be superior to placebo on the PANSS total score and the CGI-S.
Study 3 enrolled 439 subjects and involved two flexible-dose range groups of Vraylar, both of which were superior to placebo on the PANSS total score and the CGI-S.
The drug demonstrated efficacy at doses between 1.5mg/day and 9mg/day compared to placebo. The maximum recommended dose was fixed at 6mg/day, however, following the observance of certain adverse reactions with increase in the dose.
Vraylar's efficacy in the acute treatment of bipolar disorder was observed in three three-week, placebo-controlled trials. The primary and secondary efficacy measures to assess the psychiatric signs and symptoms were determined using Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity scale (CGI-S). The primary end point in each study was the decrease from baseline in YMRS total score at the end of week three.
Study 1 enrolled 492 patients and involved two flexible-dose range groups of Vraylar, both of which were found superior to placebo on the YMRS total score and the CGI-S.
Study 2 admitted 235 patients and involved a flexible dose range of the drug, which was found superior to placebo on the YMRS total score and the CGI-S.
Study 3 with 310 subjects was similar to the previous study and again demonstrated that the drug was superior to placebo.
The most common adverse reactions observed during the trials for bipolar mania included extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence and restlessness, while those observed in schizophrenia patients were extrapyramidal symptoms and akathisia.