Johnson & Johnson Announces CAPLYTA (lumateperone) Shows Significant and Rapid Improvement in Bipolar Mania in Second Pivotal Phase 3 Study

• 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
• 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., Nov. 10, 2026 /PRNewswire/ -- 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

• 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.
• 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).
• 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.
• 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.

CAPLYTA^® IMPORTANT SAFETY INFORMATION

What is CAPLYTA (lumateperone)?

CAPLYTA^® (lumateperone) is a prescription medicine used in adults along with an antidepressant to treat major depressive disorder (MDD); to treat depressive episodes associated with bipolar I or bipolar II disorder (bipolar depression) alone or with lithium or valproate; or to treat schizophrenia. It is not known if CAPLYTA is safe and effective in children.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CAPLYTA? 

• Medicines like CAPLYTA can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). CAPLYTA is not approved for treating people with dementia-related psychosis.
  
  
• CAPLYTA and antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions.
  • Patients and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when CAPLYTA or an antidepressant medicine is started or when the dose is changed.
  • Report any changes in these symptoms to your healthcare provider immediately.

Do not take CAPLYTA if you are allergic to any of its ingredients. Get emergency medical help if you are having an allergic reaction (e.g., rash, itching, hives, swelling of the tongue, lip, face, or throat).

What are the possible side effects of CAPLYTA?

CAPLYTA may cause serious side effects, including:

• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.
• Neuroleptic malignant syndrome (NMS): high fever, confusion, changes in your breathing, heart rate, and blood pressure, stiff muscles, and increased sweating; these may be symptoms of a rare but potentially fatal condition. Contact your healthcare provider or go to the emergency room if you experience signs and symptoms of NMS.
• Uncontrolled body movements (tardive dyskinesia, TD) in your face, tongue, or other body parts. TD may not go away, even if you stop taking CAPLYTA. It may also occur after you stop taking CAPLYTA.
• Problems with your metabolism including high blood sugar, diabetes, increased fat (cholesterol and triglyceride) levels in your blood and weight gain. Your healthcare provider should check your blood sugar, fat levels, and weight before you start and during your treatment with CAPLYTA.
  • Extremely high blood sugar levels can lead to coma or death. Call your healthcare provider if you have any of the following symptoms of high blood sugar: feeling very thirsty, hungry, sick to your stomach, needing to urinate more than usual, weak/tired, or confused, or your breath smells fruity.
• Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with CAPLYTA.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded, dizzy, or faint when you rise too quickly from a sitting or lying position.
• Falls. CAPLYTA may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause broken bones or other injuries.
• Seizures (convulsions).
• Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. Until you know how CAPLYTA affects you, do not drive, operate heavy machinery, or do other dangerous activities.
• Problems controlling your body temperature so that you feel too warm. Avoid getting overheated or dehydrated while taking CAPLYTA.
• Difficulty swallowing that can cause food or liquid to get into the lungs.

The most common side effects of CAPLYTA include sleepiness, dizziness, nausea, dry mouth, feeling tired, and diarrhea.

These are not all the possible side effects of CAPLYTA.

Before taking CAPLYTA, tell your healthcare provider about all of your medical conditions, including if you: have or have had heart problems or a stroke, high or low blood pressure, diabetes, or high blood sugar, problems with cholesterol, have or have had a low white blood cell count, seizures (convulsions), or kidney or liver problems.

CAPLYTA may cause fertility problems in females and males. You should notify your healthcare provider if you become pregnant or intend to become pregnant while taking CAPLYTA. There is a pregnancy registry for females who are exposed to CAPLYTA during pregnancy. CAPLYTA may cause abnormal involuntary movements and/or withdrawal symptoms in newborn babies exposed to CAPLYTA during the third trimester. Talk to your healthcare provider if you breastfeed or are planning to breastfeed as CAPLYTA passes into breast milk.

Tell your healthcare provider about all the medicines you're taking. CAPLYTA may affect the way other medicines work, and other medicines may affect how CAPLYTA works, causing possible serious side effects. Do not start or stop any medicines while taking CAPLYTA without talking to your healthcare provider. You are encouraged to report negative side effects of prescription drugs. Contact Intra-Cellular Therapies, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CAPLYTA is available in 42 mg, 21 mg, and 10.5 mg capsules.

Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide for CAPLYTA.

cp-548761v3

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.

Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.

© Johnson & Johnson and its affiliates 2026. All rights reserved.

Cautions Concerning Forward-Looking Statements 
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 related to product development and the potential benefits and treatment impact of CAPLYTA^® (lumateperone). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

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

SOURCE Johnson & Johnson