Johnson & Johnson Reports Positive CAPLYTA Phase 3 Mania Data

Titusville, New Jersey, U.S., September 21, 2026

CAPLYTA Demonstrates Rapid Reduction in Manic Symptoms

The Phase 3 Study 451 evaluated once-daily CAPLYTA 42 mg against placebo over a three-week treatment period in adults with bipolar I disorder experiencing manic episodes, including episodes with mixed features. The primary efficacy measure was the Young Mania Rating Scale (YMRS), a standardized assessment used to measure the severity of manic symptoms. At Week 3, patients receiving CAPLYTA experienced a 4.8-point greater reduction in YMRS total score compared with placebo, with an effect size of −0.69 and a p-value below 0.0001. The company reported that the difference became statistically significant as early as Day 3 and remained significant through Week 3.

The study also showed improvement in overall illness severity. CAPLYTA-treated patients demonstrated significantly greater improvement on the Clinical Global Impression–Severity (CGI-S) measure at Week 3, with a least-squares mean difference of −0.5 compared with placebo. In addition, the proportion of patients achieving a clinical response, defined as at least a 50% reduction in YMRS total score, was approximately twice as high with CAPLYTA as with placebo, at 45.8% versus 20.9%, respectively.

Safety Profile Remains Consistent With CAPLYTA

Johnson & Johnson reported that CAPLYTA was well tolerated in the Phase 3 study, with low rates of treatment discontinuation and a safety profile consistent with its established profile. Treatment-related adverse events occurring at a rate of at least 5% with CAPLYTA and at least twice the placebo rate included dry mouth, reported in 7.9% of CAPLYTA-treated patients versus 3.4% with placebo, and nausea, reported in 7.9% versus 2.3%, respectively. These findings add new clinical evidence to the established safety and tolerability experience with lumateperone. CAPLYTA is an oral, once-daily atypical antipsychotic. It is currently approved in adults for schizophrenia, depressive episodes associated with bipolar I or bipolar II disorder, and as adjunctive therapy with antidepressants for major depressive disorder. However, Johnson & Johnson specifically states that CAPLYTA is not approved for the treatment of manic episodes associated with bipolar I disorder. The Phase 3 results therefore represent investigational evidence rather than a regulatory approval for bipolar mania.

Johnson & Johnson Advances Bipolar Mania Program

The new results expand the clinical development program for CAPLYTA beyond its established use in bipolar depression. Study 451 is the first of two pivotal Phase 3 studies evaluating lumateperone in adults with manic episodes associated with bipolar I disorder. Johnson & Johnson reported that a second pivotal study, Study 452, has been completed and that data analysis is underway. The company said the findings support continued evaluation of CAPLYTA’s potential across different phases of bipolar I disorder. Bipolar disorder is characterized by recurring depressive and manic episodes, while manic episodes associated with bipolar I disorder can escalate rapidly and may require hospitalization.

The development of treatments capable of producing rapid and sustained control of manic symptoms remains an important area of pharmaceutical research. For the pharmaceutical industry, the Phase 3 findings provide additional clinical evidence for lumateperone in bipolar mania and advance Johnson & Johnson’s neuroscience development program. Further regulatory steps would be required before CAPLYTA could be approved for this investigational indication.

Source: Johnson & Johnson press release