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CAPLYTA® significantly reduced the signs and symptoms of acute manic episodes associated with bipolar I disorder as early as Day 3, with benefits sustained through Week 3
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Results build on the established efficacy, safety and tolerability profile of CAPLYTA®, further supporting its potential to reach more patients across bipolar I and II disorders
TITUSVILLE, N.J. (September 21, 2026) – Johnson & Johnson (NYSE: JNJ) today announced positive topline results from the 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 study met its primary endpoint, with CAPLYTA® demonstrating a statistically significant and rapid reduction in manic symptoms versus placebo at Week 3, with significant improvement seen as early as Day 3. The findings were presented in a late-breaking presentation at the 2026 Psych Congress Annual Meeting (September 15-19, New Orleans, LA), among 24 Johnson & Johnson neuropsychiatry presentations featured at this year’s meeting.
Bipolar disorder is a complex, lifelong condition affecting an estimated 37 million people worldwide and marked by recurring depressive and manic episodes that can profoundly affect a person’s health and daily life.1 Manic episodes, a defining feature of bipolar I disorder, can escalate quickly and often require hospitalization.2,3 Treatment options remain limited by variability in response and tolerability concerns, underscoring the need for therapies that can provide rapid and robust symptom control.
Study 451 is the first of two pivotal Phase 3 studies evaluating CAPLYTA® in adults with manic episodes associated with bipolar I disorder.4 These findings build on the established efficacy of CAPLYTA® in bipolar depression and support its potential to address both depressive and acute manic episodes associated with bipolar I disorder. CAPLYTA® is not approved for the treatment of manic episodes associated with bipolar I disorder.
“Mania is among the most dangerous and worrisome phases of bipolar disorder, and treating it effectively takes more than partial or temporary relief of symptoms; it means bringing the episode itself under control as quickly as possible,” said Michael E. Thase, M.D., Professor of Psychiatry and Chief, Division of Mood and Anxiety Disorders Treatment & Research Program, University of Pennsylvania.a “These results are encouraging because CAPLYTA® not only significantly improved the symptoms of mania, but did so as early as Day 3, with benefits sustained through Week 3, supporting its potential to meaningfully advance how we treat acute mania in bipolar I disorder.”
The Phase 3 randomized, double-blind study evaluated once-daily CAPLYTA® 42mg versus placebo over three weeks in adults with manic episodes, with or without mixed features, associated with bipolar I disorder (Study 451; NCT06462586).4
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Rapid improvement in manic symptoms: The study met the primary endpoint, with CAPLYTA® demonstrating a statistically significant 4.8-point greater reduction in Young Mania Rating Scale (YMRS) total score versus placebo at Week 3 (effect size −0.69; p<.0001). Significant improvement was observed as early as Day 3 and sustained through Week 3.
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Improvement in overall illness severity: Patients treated with CAPLYTA® also showed significantly greater improvement in overall illness severity versus placebo at Week 3, as measured by the Clinical Global Impression–Severity (CGI-S) score, a key secondary endpoint (least-squares mean difference [LSMD], –0.5; P<.0001).
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Greater clinical response: Twice as many patients treated with CAPLYTA® achieved clinical response, defined as a ≥50% reduction in YMRS total score, compared to placebo (45.8% vs. 20.9%; p<.0001).
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Safety and tolerability consistent with established profile: 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 dry mouth (7.9% vs. 3.4%) and nausea (7.9% vs. 2.3%).
“Bipolar I disorder is a lifelong, cycling illness, and managing it means navigating both manic and depressive episodes over time, each with distinct treatment needs,” said Jane Tiller, Vice President, Global Head of Development, Neuroscience, Johnson & Johnson. “These Phase 3 results build on the established efficacy of CAPLYTA® in bipolar depression and represent an important step in evaluating its potential to address both depressive and acute manic episodes associated with bipolar I disorder.”
A second pivotal Phase 3 study (Study 452) evaluating CAPLYTA® for the treatment of manic episodes in adults with bipolar I disorder has been completed, and data analysis is underway.
Editor’s Note
a Michael E. Thase, M.D., Professor of Psychiatry and Chief, Division of Mood and Anxiety Disorders Treatment & Research Program, University of Pennsylvania, has provided consulting, advisory, and speaking services to Johnson & Johnson. He has not been paid for any media work.
ABOUT BIPOLAR MANIA
Bipolar disorder affects an estimated 37 million people worldwide.1 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.2 Symptoms of mania can include grandiosity, decreased need for sleep, racing thoughts, distractibility, and risk-taking behavior.2 Manic episodes can escalate quickly, often requiring hospitalization for safety and treatment.3 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.1 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
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World Health Organization. Bipolar disorder. September 2025. Accessed August 2026. https://www.who.int/news-room/fact-sheets/detail/bipolar-disorder
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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.
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Cleveland Clinic. Mania. April 2026. Accessed August 2026. https://my.clevelandclinic.org/health/diseases/21603-mania
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CAPLYTA BPM poster Cutler A.J., Earley, W.R., Hayes, R et al. Lumateperone Treatment of Manic Episodes With or Without Mixed Features in Bipolar I disorder: Results From a Double-Blind, Placebo-Controlled, Randomized, Phase 3 Trial. Psych Congress 2026; September 15-19, 2026. Poster 72.