Lumateperone Shows Significant and Rapid Improvement in Bipolar Mania

Johnson & Johnson today announced that Study 452, the second pivotal phase 3 study evaluating lumateperone (Caplyta) for the treatment of manic episodes with or without mixed features in adults with bipolar I disorder, met its primary and key secondary endpoints. Caplyta significantly improved manic symptoms and overall illness severity compared with placebo at week 3, with significant improvements seen as early as day 3.¹ The results were featured as a late-breaking presentation at the 2026 Neuroscience Education Institute (NEI) Fall Congress in Colorado Springs, CO.

Together with the positive results from Study 451,² these findings provide consistent evidence across 2 pivotal phase 3 studies and will support the planned US regulatory submission.

“Manic episodes can disrupt a person’s safety, relationships, and daily life within days, underscoring the need for treatments that act rapidly,” said Jane Tiller, FRCPsych, the vice president and global head of Development, Neuroscience, at Johnson & Johnson. “Building on the established safety and efficacy profile of CAPLYTA in bipolar I and II depression, consistent, positive results across 2 pivotal phase 3 studies in acute mania associated with bipolar I disorder support its potential to help stabilize symptoms for patients during some of the most difficult moments of their illness.”

More About Study 452

Study 452 was a global, phase 3 randomized, double-blind study evaluating once-daily Caplyta 42 mg vs placebo over 3 weeks in adults with manic episodes, with or without mixed features, associated with bipolar I disorder (NCT06462612).¹

Caplyta demonstrated a statistically significant improvement in Young Mania Rating Scale (YMRS) total score, with 3.7-point greater reduction compared with placebo at week 3 (effect size −0.43; P<.0001). Significant improvement was observed as early as day 3 and sustained through week 3.

Additionally, nearly twice as many patients achieved a clinical response at week 3, with 43.9% of patients receiving Caplyta seeing at least a 50% improvement from baseline on the YMRS total score compared with 23.7% receiving placebo (P<.0001).

The key secondary endpoint was also met, with significantly greater improvement on the Clinical Global Impression–Severity (CGI-S) score vs placebo at week 3 (LSMD −0.41; P=.0003), with improvement observed as early as day 3.

Safety and Tolerability

Caplyta was well-tolerated, with low rates of discontinuation and a safety profile consistent with its established profile. The most common treatment-related adverse events reported at a rate of at least 5% with Caplyta and at least twice the rate of placebo were dizziness, dry mouth, and somnolence/sedation.

References

1. Johnson & Johnson announces CAPLYTA (lumateperone) shows significant and rapid improvement in bipolar mania in second pivotal phase 3 study. News release. November 10, 2026. Accessed November 10, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-caplyta-lumateperone-shows-significant-and-rapid-improvement-in-bipolar-mania-in-second-pivotal-phase-3-study

2. CAPLYTA^® (lumateperone) shows significant and rapid improvement in bipolar mania in pivotal phase 3 study. News release. September 21, 2026. Accessed November 10, 2026. https://www.jnj.com/media-center/press-releases/caplyta-lumateperone-shows-significant-and-rapid-improvement-in-bipolar-mania-in-pivotal-phase-3-study