Supplemental new drug application submitted to U.S. FDA for CAPLYTA® (lumateperone) with data demonstrating significant schizophrenia relapse prevention compared to placebo
Johnson & Johnson (NYSE:JNJ) has submitted a supplemental New Drug Application (sNDA) to the FDA for CAPLYTA® (lumateperone) based on impressive Phase 3 trial results in schizophrenia relapse prevention. The study demonstrated a 63% reduction in relapse risk compared to placebo, with significantly longer time to relapse during the 26-week double-blind treatment phase (p=0.0002).
The trial's safety profile remained consistent with existing clinical data, with headache being the most common adverse event. CAPLYTA® is already FDA-approved for schizophrenia treatment and is the first approved therapy for both bipolar I and II depression. The drug's mechanism involves high serotonin 5-HT2A receptor occupancy and lower dopamine D2 receptor occupancy at therapeutic doses.
Johnson & Johnson (NYSE:JNJ) ha presentato una domanda supplementare di nuovo farmaco (sNDA) alla FDA per CAPLYTA® (lumateperone), basata su risultati impressionanti di uno studio di Fase 3 sulla prevenzione delle ricadute nella schizofrenia. Lo studio ha mostrato una riduzione del rischio di ricaduta del 63% rispetto al placebo, con un tempo significativamente più lungo prima della ricaduta durante la fase di trattamento in doppio cieco di 26 settimane (p=0,0002).
Il profilo di sicurezza del trial è rimasto coerente con i dati clinici esistenti, con il mal di testa come evento avverso più comune. CAPLYTA® è già approvato dalla FDA per il trattamento della schizofrenia ed è la prima terapia approvata per la depressione bipolare di tipo I e II. Il meccanismo d'azione del farmaco coinvolge un'elevata occupazione del recettore serotoninergico 5-HT2A e una minore occupazione del recettore dopaminergico D2 a dosi terapeutiche.
Johnson & Johnson (NYSE:JNJ) ha presentado una solicitud suplementaria de nuevo medicamento (sNDA) a la FDA para CAPLYTA® (lumateperona), basada en resultados impresionantes de un ensayo de Fase 3 para la prevención de recaídas en la esquizofrenia. El estudio demostró una reducción del riesgo de recaída del 63% en comparación con el placebo, con un tiempo significativamente mayor hasta la recaída durante la fase de tratamiento doble ciego de 26 semanas (p=0,0002).
El perfil de seguridad del ensayo se mantuvo consistente con los datos clínicos existentes, siendo el dolor de cabeza el evento adverso más común. CAPLYTA® ya está aprobado por la FDA para el tratamiento de la esquizofrenia y es la primera terapia aprobada para la depresión bipolar tipo I y II. El mecanismo del fármaco implica una alta ocupación del receptor de serotonina 5-HT2A y una menor ocupación del receptor de dopamina D2 a dosis terapéuticas.
Johnson & Johnson (NYSE:JNJ)는 조현병 재발 예방에 대한 인상적인 3상 임상시험 결과를 바탕으로 CAPLYTA® (루마테페론)의 보충 신약 신청서(sNDA)를 FDA에 제출했습니다. 연구 결과, 위약 대비 재발 위험이 63% 감소했으며, 26주간 이중맹검 치료 기간 동안 재발까지의 시간이 유의하게 연장되었습니다(p=0.0002).
임상시험의 안전성 프로파일은 기존 임상 데이터와 일관되었으며, 두통이 가장 흔한 부작용으로 나타났습니다. CAPLYTA®는 이미 FDA로부터 조현병 치료제로 승인받았으며, 양극성 장애 I형 및 II형 우울증 모두에 승인된 최초의 치료제입니다. 이 약물의 작용 기전은 치료 용량에서 세로토닌 5-HT2A 수용체 점유율이 높고 도파민 D2 수용체 점유율이 낮은 것을 포함합니다.
Johnson & Johnson (NYSE:JNJ) a soumis une demande supplémentaire de nouveau médicament (sNDA) à la FDA pour CAPLYTA® (lumatéperone), basée sur des résultats impressionnants d'un essai de phase 3 pour la prévention des rechutes de la schizophrénie. L'étude a démontré une réduction de 63 % du risque de rechute par rapport au placebo, avec un délai significativement plus long avant la rechute pendant la phase de traitement en double aveugle de 26 semaines (p=0,0002).
Le profil de sécurité de l'essai est resté conforme aux données cliniques existantes, les maux de tête étant l'événement indésirable le plus fréquent. CAPLYTA® est déjà approuvé par la FDA pour le traitement de la schizophrénie et est la première thérapie approuvée pour la dépression bipolaire de type I et II. Le mécanisme d'action du médicament implique une forte occupation des récepteurs sérotoninergiques 5-HT2A et une occupation moindre des récepteurs dopaminergiques D2 à des doses thérapeutiques.
Johnson & Johnson (NYSE:JNJ) hat einen ergänzenden Antrag auf Zulassung eines neuen Medikaments (sNDA) bei der FDA für CAPLYTA® (Lumateperon) eingereicht, basierend auf beeindruckenden Ergebnissen der Phase-3-Studie zur Rückfallprävention bei Schizophrenie. Die Studie zeigte eine 63%ige Reduktion des Rückfallrisikos im Vergleich zu Placebo, mit einer signifikant längeren Zeit bis zum Rückfall während der 26-wöchigen doppelblinden Behandlungsphase (p=0,0002).
Das Sicherheitsprofil der Studie entsprach den bestehenden klinischen Daten, wobei Kopfschmerzen das häufigste unerwünschte Ereignis waren. CAPLYTA® ist bereits von der FDA zur Behandlung der Schizophrenie zugelassen und die erste zugelassene Therapie für bipolare Depression Typ I und II. Der Wirkmechanismus des Medikaments beinhaltet eine hohe Besetzung des Serotonin-5-HT2A-Rezeptors und eine geringere Besetzung des Dopamin-D2-Rezeptors bei therapeutischen Dosen.
- Phase 3 trial showed significant 63% reduction in schizophrenia relapse risk vs placebo
- Significantly delayed time to all-cause discontinuation compared to placebo
- Favorable safety profile with no new safety concerns identified
- No titration required - patients can start at effective dose with or without food
- Exact mechanism of action remains unknown
- Common adverse events include somnolence/sedation, dizziness, nausea, and dry mouth
Insights
JNJ's CAPLYTA sNDA submission shows strong 63% reduction in schizophrenia relapse risk, expanding their already comprehensive CNS portfolio.
Johnson & Johnson has submitted a supplemental New Drug Application (sNDA) to the FDA for CAPLYTA® (lumateperone) with compelling Phase 3 data showing a 63% reduction in schizophrenia relapse risk versus placebo. The study demonstrated significantly longer time to relapse during the 26-week double-blind treatment phase (p=0.0002) and delayed time to all-cause discontinuation (p=0.0007).
This regulatory submission strengthens JNJ's CNS portfolio strategic position in three important ways. First, it expands CAPLYTA's clinical utility beyond its current FDA approvals for schizophrenia and bipolar I/II depression. Second, it addresses a critical unmet need in schizophrenia management - relapse prevention - with patients experiencing an average of nine relapses in less than six years. Third, it differentiates JNJ in the competitive landscape by offering what they describe as "the broadest range of oral and long-acting injectable treatment options" for schizophrenia.
CAPLYTA's favorable tolerability profile is particularly notable in the antipsychotic market. The drug demonstrated placebo-like effects on weight, metabolism, and extrapyramidal symptoms in short-term studies - side effects that commonly drive discontinuation. Its once-daily dosing without titration requirements also enhances its commercial profile.
Beyond schizophrenia, JNJ has additional regulatory momentum with CAPLYTA, as an sNDA for adjunctive treatment in major depressive disorder is already under FDA review, potentially expanding its addressable market to another high-prevalence indication.
Submission is based on long-term Phase 3 data demonstrating 63 percent reduction in risk of relapse in adults with schizophrenia compared to placebo
CAPLYTA® is FDA approved to treat schizophrenia and is the first and only approved treatment for bipolar I and II depression as an adjunctive and monotherapy
With the addition of CAPLYTA® to Johnson & Johnson's robust portfolio of therapies, the Company now offers the broadest range of treatment options for adults with schizophrenia
"For people living with schizophrenia, relapses can be devastating as they disrupt lives, undo hard-earned treatment progress toward patients' goals, and increase the risk of hospitalization with each episode," said Christoph U. Correll, M.D., Clinical Professor of Psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York.a "CAPLYTA® substantially lowers the chance of relapse for patients compared to placebo, which is often a major source of anxiety and suffering for them and their families."
The submission is supported by positive results from a Phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal trial, which on the primary endpoint found time to relapse during the 26-week double-blind treatment phase was significantly longer in patients receiving CAPLYTA® compared to those receiving placebo (p=0.0002). Treatment with CAPLYTA® was also associated with a 63 percent reduction in risk of relapse versus placebo (hazard ratio [
Schizophrenia affects up to an estimated 2.8 million adults in
"Relapse prevention is a critical goal for the long-term care and management of this debilitating disorder," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine. "These Phase 3 results provide compelling evidence of meaningful relapse prevention, which is critical in preserving long-term patient stability, breaking the cycle of hospitalization, and helping to control symptom progression. We're committed to building on the decade of research reinforcing the robust efficacy, proven safety, and favorable tolerability of CAPLYTA® and providing additional data to support the long-term use of this medicine in neuropsychiatric disorders."
While its exact mechanism of action is unknown, CAPLYTA® is characterized by high serotonin 5-HT2A receptor occupancy and lower amounts of dopamine D2 receptor occupancy at therapeutic doses. In short-term clinical studies, CAPLYTA® was similar to placebo in weight change, metabolic effects, and extrapyramidal symptoms, which are often cited as reasons for treatment discontinuation. The most commonly reported adverse events were somnolence/sedation, dizziness, nausea, and dry mouth. CAPLYTA® can be taken at any time of day with or without food and does not require titration, allowing adult patients to start treatment at the effective dose.
CAPLYTA® is FDA approved for the treatment of schizophrenia, as well as depressive episodes associated with bipolar I or II disorder in adults, as monotherapy, and as adjunctive therapy with lithium or valproate. An sNDA for CAPLYTA® as an adjunctive treatment for adults with major depressive disorder (MDD) is currently under FDA review. If approved, CAPLYTA® has the potential to become a new standard of care to treat some of today's most prevalent and debilitating mental health disorders.
Editor's note:
a. Christoph U. Correll, M.D., has provided consulting, advisory, and speaking services to Johnson & Johnson. He has not been paid for any media work.
About Schizophrenia
Schizophrenia is a complex, chronic brain disorder that affects how people think, feel, speak, and act. It affects up to an estimated 2.8 million adults in
About Study 304
This study was a multicenter, multi-national, double-blind, placebo-controlled, randomized withdrawal study of lumateperone for the prevention of symptomatic relapse in adult patients with schizophrenia. The approximately 47-week study included an 18-week open-label phase where patients with schizophrenia were treated with lumateperone 42 mg per day. Patients who met the stabilization criteria during the open-label period progressed to the double-blind treatment phase. These patients were randomized to continue on lumateperone 42 mg (N=114) or switched to placebo (N=114) for up to 26 weeks or until the time to relapse occurred. The primary endpoint was time to first symptom relapse and the key secondary endpoint was time to all cause discontinuation during the double-blind phase.
About CAPLYTA® (lumateperone)
CAPLYTA® 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy, and as adjunctive therapy with lithium or valproate. 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 postsynaptic antagonist activity at central dopamine D2 receptors.
CAPLYTA® is under FDA review for potential approval as an adjunctive treatment for adults with major depressive disorder and is being studied for other neuropsychiatric and neurological disorders. CAPLYTA® is not FDA-approved for these disorders.
CAPLYTA® (lumateperone) is indicated in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.
Important Safety Information
Boxed Warnings:
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.
- Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.
Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.
Warnings & Precautions: Antipsychotic drugs have been reported to cause:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.
- Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.
- Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.
- Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.
- Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.
- Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.
- Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.
- Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
- Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.
- Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.
- Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.
Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors.
Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Dose reduction is recommended for patients with moderate or severe hepatic impairment.
Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.
CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules.
Please click here to see full Prescribing Information including Boxed Warnings.
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 2025. 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 regarding product development and the potential benefits and treatment impact of CAPLYTA®. 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 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
i Intra-Cellular Therapies Announces Positive Topline Results in Phase 3 Trial Evaluating CAPLYTA for the Prevention of Relapse in Patients with Schizophrenia. GlobeNewswire, 05 Nov. 2024, https://www.globenewswire.com/news-release/2024/11/05/2974784/30597/en/Intra-Cellular-Therapies-Announces-Positive-Topline-Results-in-Phase-3-Trial-Evaluating-CAPLYTA-for-the-Prevention-of-Relapse-in-Patients-with-Schizophrenia.html.
ii "Schizophrenia Fact Sheet." Treatment Advocacy Center, 10 Mar. 2025, www.tac.org/reports_publications/schizophrenia-fact-sheet/.
iii Alphs L, et al. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable therapy. Int Clin Psychopharmacol. 2016;31(4)202-209. doi:10.1097/YIC.0000000000000125
iv Lafeuille MH, Gravel J, Lefebvre P, et al. Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics. J Med Econ. 2013;16(11):1290-1299. doi: 10.3111/13696998.2013.841705
v Birchwood, M. "Early intervention and sustaining the management of vulnerability." The Australian and
vi Tandon, Rajiv et al. "The schizophrenia syndrome, circa 2024: What we know and how that informs its nature." Schizophrenia research vol. 264 (2024): 1-28. doi:10.1016/j.schres.2023.11.015
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SOURCE Johnson & Johnson
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