The US Food and Drug Administration has approved lumateperone (CAPLYTA), a once-daily oral treatment, as adjunctive therapy to antidepressants for adults with major depressive disorder (MDD), Johnson & Johnson announced today. This marks the fourth indication for the atypical antipsychotic and the first approval under Johnson & Johnson leadership since acquiring Intra-Cellular Therapies, Inc.
Approval was based on two positive phase 3 global, double-blind, placebo-controlled trials (Study 501 and Study 502) that met their primary and key secondary endpoints Lumateperone demonstrated a separation from placebo on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 6 weeks, with mean separations of -4.9 and -4.5 points in Studies 501 and 502, respectively. Separation from placebo was observed as early as 1 week in Study 501 and 2 weeks in Study 502. Both trials also demonstrated statistically significant reductions in Clinical Global Impression Scale-Severity index (CGI-S) scores at 6 weeks: -0.7 points in Study 501 and -0.5 points in Study 502.
"For people who are still experiencing lingering depressive symptoms while on an antidepressant, adding CAPLYTA to a patient's treatment regimen may offer early improvement, with the potential for remission—the ultimate goal of treatment," said Roger S. McIntyre, MD, Professor of Psychiatry and Pharmacology at the University of Toronto.
The safety profile was consistent with previous indications for schizophrenia and bipolar depression. Rates of weight gain, metabolic changes (lipid and glucose levels), akathisia, and restlessness were similar to placebo. The most common adverse events observed at a rate greater than or equal to 5% for lumateperone and greater than twice the rate of placebo were dizziness, dry mouth, somnolence/sedation, nausea, fatigue, and diarrhea.
In a 26-week open-label extension safety study (Study 503), 80% of patients responded to treatment and 65% achieved remission (defined as MADRS total score less than or equal to 10) at 6 months. The safety profile remained consistent with the pivotal studies, with minimal changes in body morphology, cardiometabolic laboratory values, prolactin levels, pulse rate, blood pressure, and electrocardiogram measures.
Lumateperone is administered at a fixed dose of 42 mg without the need for titration. While its exact mechanism of action is unknown, efficacy is thought to be mediated through antagonist activity at central serotonin 5-HT₂A receptors and partial agonist activity at central dopamine D₂ receptors.
The medication was previously approved for the treatment of schizophrenia in adults and for depressive episodes associated with bipolar I or II disorder, both as monotherapy and as adjunctive therapy with lithium or valproate. A supplemental New Drug Application for relapse prevention in schizophrenia was recently submitted to the FDA.
Source: Johnson & Johnson