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Submission is based on long-term Phase 3 data demonstrating 63 percent reduction in risk of relapse in adults with schizophrenia compared to placebo
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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
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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
TITUSVILLE, N.J. (July 8, 2025) – Johnson & Johnson (NYSE:JNJ) announced today the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) based upon long-term data evaluating the safety and efficacy of CAPLYTA® (lumateperone) for the prevention of relapse in schizophrenia. CAPLYTA® is the newest addition to Johnson & Johnson’s portfolio of schizophrenia therapies, which now offers the broadest range of oral and long-acting injectable treatment options to support each patient’s individual treatment journey.
“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 [95% CI] = 0.37, [0.22, 0.65]). The key secondary endpoint showed a significantly delayed time to all-cause discontinuation, including relapse, compared with placebo during the double-blind phase (p=0.0007). The safety profile of CAPLYTA® was consistent with the existing body of clinical data, and no new safety concerns were identified. The most commonly reported adverse event that was observed at a rate greater than or equal to 5% and twice the rate of placebo was headache.i
Schizophrenia affects up to an estimated 2.8 million adults in the United States, yet it remains insufficiently treated, with approximately 40 percent of people not receiving care.ii When left untreated, this complex mental health disorder can lead to episodes of psychosis, hallucinations, or other disruptive behaviors, which can damage and interrupt the lives of those living with schizophrenia as well as their loved ones.iii Relapses, or a recurrence of symptoms, are associated with significant functional decline, increased caregiver burden, and a greater likelihood of hospitalization.iii On average, an adult with schizophrenia experiences nine relapses in less than six years.iv
“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 the United States yet remains widely misunderstood and insufficiently treated.ii Symptoms vary by person, but confusion and distortions in perceptions, emotions, and behavior are common. Evidence shows that the first three to five years after diagnosis – “the critical period” – from symptom onset are key for a patient’s treatment, as this is when the condition progresses most rapidly.v,vi A comprehensive treatment plan, which may include medication, therapy, and psychosocial services, can be critical in delaying the time to relapse for adults with schizophrenia.iii
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.
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
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 New Zealand journal of psychiatry vol. 34 Suppl (2000): S181-4. doi:10.1080/000486700241
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