Johnson & Johnson announced on November 10 that Caplyta (lumateperone) met the primary and key secondary endpoints of Study 452, the second pivotal Phase 3 trial of the drug in manic episodes with or without mixed features in adults with bipolar I disorder. Together with the earlier positive Study 451, the company said the results will support a planned United States regulatory submission for bipolar mania, an indication Caplyta does not yet hold.
In Study 452, a global randomized, double-blind trial of once-daily Caplyta 42 mg against placebo over three weeks, mania scores on the Young Mania Rating Scale fell 3.7 points more on the drug than on placebo at week 3, an effect size of minus 0.43 with a p-value below 0.0001. The separation appeared as early as day 3 and held through the end of dosing. Response, defined as at least a 50 percent improvement in the mania score, was achieved by 43.9 percent of Caplyta patients against 23.7 percent on placebo. The key secondary endpoint, overall illness severity on the Clinical Global Impression Severity scale, also favored the drug, with a difference of minus 0.41 points and a p-value of 0.0003.
The result is consistent with Study 451, where Fierce Pharma reported a 4.8-point advantage on the same mania scale and response rates of 45.8 percent against 20.9 percent. Two concordant pivotal trials are the standard evidentiary package for a label expansion filing, and Johnson & Johnson said the combined data will support its planned submission to the Food and Drug Administration.
Caplyta is already approved in the United States for schizophrenia, for depressive episodes associated with bipolar I or II disorder, and as an add-on treatment for major depressive disorder. A mania approval would make it one of the few antipsychotics spanning both the depressive and manic poles of bipolar disorder, widening the commercial base of a franchise Johnson & Johnson acquired with Intra-Cellular Therapies.
On safety, the company said tolerability was consistent with prior studies, with low discontinuation rates. The most common treatment-related adverse events, reported in at least 5 percent of Caplyta patients and at least twice the placebo rate, were dizziness, dry mouth and somnolence or sedation. The detailed data were presented as a late-breaking poster at the Neuroscience Education Institute Fall Congress in Colorado Springs, held November 5 to 8. Bipolar disorder affects an estimated 36 million people worldwide, according to the World Health Organization figures cited by the company, and manic episodes frequently require hospitalization.