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CAPLYTA improved manic symptoms versus placebo as early as Day 3, with improvement sustained through Week 3 and a safety and tolerability profile consistent with prior studies
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Two positive Phase 3 studies will support a planned U.S. FDA submission of CAPLYTA for bipolar mania, reinforcing its potential to address both depressive and manic episodes of bipolar disorder
New Brunswick, N.J. (November 10, 2026) – Johnson & Johnson (NYSE: JNJ) today announced that Study 452, the second pivotal Phase 3 study evaluating CAPLYTA (lumateperone) 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 versus placebo at Week 3, with significant improvements observed as early as Day 3.1 The results were featured as a late-breaking presentation at the 2026 Neuroscience Education Institute (NEI) Fall Congress (November 5-8, Colorado Springs, CO).
Together with the positive results from Study 451, these findings provide consistent evidence across two pivotal Phase 3 studies and will support the planned U.S. 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, Vice President, Global Head of Development, Neuroscience, Johnson & Johnson. “Building on the established safety and efficacy profile of CAPLYTA in bipolar I and II depression, consistent, positive results across two 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.”
Study 452 demonstrated rapid and sustained improvement in manic symptoms
Study 452 was a global, Phase 3 randomized, double-blind study evaluating once-daily CAPLYTA 42 mg versus placebo over three weeks in adults with manic episodes, with or without mixed features, associated with bipolar I disorder (NCT06462612).1
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Primary endpoint met: CAPLYTA demonstrated a statistically significant improvement in Young Mania Rating Scale (YMRS) total score, with 3.7-point greater reduction versus placebo at Week 3 (effect size −0.43; P<.0001). Significant improvement was observed as early as Day 3 and sustained through Week 3.
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Nearly twice as many patients achieved a clinical response at Week 3: 43.9% of patients receiving CAPLYTA had at least a 50% improvement from baseline on the YMRS total score compared to 23.7% receiving placebo (P<.0001).
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Benefit extended to overall illness severity: The key secondary endpoint was met, with significantly greater improvement on the Clinical Global Impression–Severity (CGI-S) score versus placebo at Week 3 (LSMD −0.41; P=.0003), with improvement observed as early as Day 3.
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Tolerability was consistent with prior studies: 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 (AEs) 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.
ABOUT BIPOLAR MANIA
Bipolar disorder affects an estimated 36 million people worldwide.2 Mania is a defining feature of bipolar I disorder—a period of abnormally elevated or irritable mood and/or increased energy or activity that most people experience alongside depressive episodes over the course of the illness.3 Symptoms of mania can include grandiosity, decreased need for sleep, racing thoughts, distractibility, and risk-taking behavior.3 Manic episodes can escalate quickly, often requiring hospitalization for safety and treatment.4 These noticeable behavioral changes often differ markedly from an individual’s baseline and can have serious consequences for a person’s safety, relationships, career, and finances, contributing to its standing as one of the leading causes of disability worldwide.2 Rapid and sustained control of manic symptoms remains an important treatment goal in the management of bipolar I disorder.
ABOUT CAPLYTA (lumateperone)
CAPLYTA is an oral, once daily atypical antipsychotic approved by the U.S. Food and Drug Administration in adults for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy or as adjunctive therapy with lithium or valproate; for the treatment of schizophrenia; and as adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD).
CAPLYTA is not approved for the treatment of manic episodes associated with bipolar I disorder.
While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and partial agonist activity at central dopamine D2 receptors.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity.
Footnotes
1 McIntyre R.S., Earley W.R., Hayes R. et al. Lumateperone for the treatment of bipolar mania in patients with bipolar I disorder: results from a double-blind, placebo controlled, randomized, Phase 3 trial. NEI Fall Congress 2026; November 5-8, 2026. Poster 98.
2 World Health Organization. Bipolar disorder. September 2025. Accessed November 2026. https://www.who.int/news-room/fact-sheets/detail/bipolar-disorder
3 Oliva V., Fico G,. De Prisco M. et al. Bipolar disorders: an update on critical aspects. The Lancet Regional Health. 2024;48. doi:10.1016/j.lanepe.2024.101135.
4 Cleveland Clinic. Mania. April 2026. Accessed November 2026. https://my.clevelandclinic.org/health/diseases/21603-mania