Titusville, New Jersey, U.S., September 21, 2026
Johnson & Johnson has announced positive topline results from a pivotal Phase 3 study evaluating CAPLYTA® (lumateperone) for the treatment of manic episodes, with or without mixed features, in adults with bipolar I disorder. The randomized, double-blind study met its primary endpoint, showing that once-daily CAPLYTA 42 mg produced a statistically significant reduction in manic symptoms compared with placebo after three weeks of treatment. Importantly, improvement was observed as early as Day 3 and was sustained through Week 3, adding new clinical evidence to the established use of lumateperone in bipolar depression. CAPLYTA is not currently approved for the treatment of manic episodes associated with bipolar I disorder.
Phase 3 Study Shows Rapid Reduction in Mania Symptoms
The Phase 3 Study 451 enrolled adults experiencing manic episodes associated with bipolar I disorder, including episodes with mixed features. Participants were randomized to receive CAPLYTA 42 mg once daily or placebo during a three-week double-blind treatment period. The primary endpoint was the change from baseline in the Young Mania Rating Scale (YMRS) total score at Week 3. CAPLYTA demonstrated a 4.8-point greater reduction in YMRS score compared with placebo, with an effect size of -0.69 and a statistical significance of p<0.0001. Johnson & Johnson reported that the improvement was already statistically significant by Day 3 and remained evident throughout the three-week study period.
The results also showed improvements beyond the primary measure of manic symptoms. Participants receiving CAPLYTA experienced a significantly greater improvement in overall illness severity at Week 3, measured using the Clinical Global Impression–Severity (CGI-S) scale. The least-squares mean difference versus placebo was -0.5, with p<0.0001. In addition, 45.8% of participants treated with CAPLYTA achieved a clinical response, defined as at least a 50% reduction in YMRS score, compared with 20.9% of participants receiving placebo. These findings provide additional measures of the treatment effect observed in the pivotal study.
Safety Profile Remains Consistent With CAPLYTA
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Johnson & Johnson reported that CAPLYTA was generally well tolerated in the Phase 3 study, with low rates of treatment discontinuation and a safety profile consistent with its established clinical experience. The most common treatment-related adverse events occurring at a rate of at least 5% and at least twice that observed with placebo were dry mouth and nausea, each reported in 7.9% of CAPLYTA-treated participants compared with 3.4% and 2.3%, respectively, for placebo. The company said these findings were consistent with the established safety and tolerability profile of lumateperone.
CAPLYTA is an oral, once-daily atypical antipsychotic that is already approved in the United States for adults with depressive episodes associated with bipolar I or bipolar II disorder, schizophrenia, and as adjunctive therapy with antidepressants for major depressive disorder. The current Phase 3 program is evaluating whether its clinical utility can extend to acute manic episodes associated with bipolar I disorder. The company emphasized that the new indication remains investigational and that CAPLYTA has not been approved for bipolar mania.
Johnson & Johnson Advances Bipolar Mania Program
The latest findings represent the first of two pivotal Phase 3 studies evaluating CAPLYTA in adults with manic episodes associated with bipolar I disorder. Johnson & Johnson said the second pivotal study, Study 452, has been completed and its data analysis is underway. The company is evaluating the results as part of a broader development strategy aimed at addressing both depressive and manic episodes associated with bipolar I disorder. Bipolar disorder is a chronic psychiatric condition characterized by recurring mood episodes, while mania is a defining feature of bipolar I disorder and can involve elevated or irritable mood, increased energy, reduced need for sleep, racing thoughts, distractibility, and risk-taking behavior. The company estimates that bipolar disorder affects approximately 37 million people worldwide. The new Phase 3 findings therefore add to the clinical evidence surrounding lumateperone as Johnson & Johnson continues to evaluate its potential across different phases of mood disorders.
Source: Johnson & Johnson press release
