FDA Approves sNDA of Caplyta for the Prevention of Relapse in Schizophrenia

The US Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) based on long-term data evaluating the safety and efficacy of Johnson & Johnson’s lumateperone (Caplyta) for the prevention of relapse in schizophrenia, further reinforcing the long-term efficacy and tolerability of Caplyta.¹

In the phase 3, double-blind, randomized withdrawal trial supporting this update, Caplyta significantly extended time to relapse vs placebo during the 26-week double-blind treatment period (P=0.0002), helping support long-term stability for adults living with schizophrenia. Participants treated with Caplyta had a 63% lower risk of relapse compared with placebo (hazard ratio = 0.37), and 84% of participants were relapse-free over 6 months. Caplyta also significantly delayed time to all-cause treatment discontinuation, including relapse.

"Relapse can be one of the most disruptive aspects of schizophrenia, often undoing hard-won progress and increasing the risk of hospitalization," said Christoph U. Correll, MD, a clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York. "These phase 3 results—showing significantly longer time to relapse with 84% remaining relapse free over 6-months—provide clinicians with another tool that can offer long-term stability for people living with schizophrenia."

In terms of safety, Caplyta’s safety profile remained consistent with the existing body of clinical data, and no new safety concerns were identified. The most common treatment-related adverse event was headache, which occurred in at least 5% of participants and at least twice the rate of placebo.²

Caplyta’s exact mechanism of action is unknown; however, it is characterized by high serotonin 5-HT2A receptor occupancy and moderate amounts of dopamine D2 receptor occupancy at therapeutic doses. In schizophrenia short-term clinical studies, Caplyta was comparable with placebo in weight change, metabolic effects, and extrapyramidal symptoms—this is important, as these are often cited by patients as reasons for discontinuing treatment. In the phase 3, 6-month randomized withdrawal, double-blind, placebo-controlled study, there were no clinically relevant increases in prolactin or cardiometabolic parameters at the end of the double-blind treatment period. Additionally, long-term data from a 12-month open-label extension study in schizophrenia showed that participants treated with Caplyta experienced a mean weight change of –2.05 kg (–4.52 lbs) over 1 year, with sustained improvements or stability in metabolic parameters.

"People living with schizophrenia deserve treatment options that help support stability over time, not just symptom control in the short term," said Celine Goldberger, MD, PhD, the vice president global medical affairs, neuroscience, innovative medicine, at Johnson & Johnson. "This label update—backed by long-term phase 3 data demonstrating a significant delay in time to relapse—reinforces our commitment to advancing evidence-based therapies to support each patient's individual needs including a proven therapy that supports stability over time."

Caplyta (lumateperone) is currently FDA approved in adults as an adjunctive therapy with antidepressants for major depressive disorder, schizophrenia, and depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy, and as adjunctive therapy with lithium or valproate. Caplyta is also being evaluated in clinical studies for other neuropsychiatric and neurological conditions beyond its current FDA-approved indications.

Relapse in schizophrenia is critical to address, as it can be associated with progressive functional deterioration, declining treatment response, worsening clinical outcomes, and an increased caregiver burden.^3,4 This could provide patients with schizophrenia a dependable option to help maintain stability.

References

1. FDA approves CAPLYTA® (lumateperone) sNDA with robust new data supporting reduced risk of relapse in schizophrenia. News release. April 27, 2026. Accessed April 27, 2026. https://www.prnewswire.com/news-releases/fda-approves-caplyta-lumateperone-snda-with-robust-new-data-supporting-reduced-risk-of-relapse-in-schizophrenia-302753851.html

2. Intra-Cellular Therapies announces positive topline results in phase 3 trial evaluating Caplyta for the prevention of relapse in patients with schizophrenia. GlobeNewswire. November 5, 2024. Accessed April 27, 2026. 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

3. Hong J, Windmeijer F, Novick D, et al. The cost of relapse in patients with schizophrenia in the European SOHO (Schizophrenia Outpatient Health Outcomes) study. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(5):835-841.

4. Almond S, Knapp M, Francois C, et al. Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry. 2004;184:346-351.