FDA approves Caplyta (lumateperone) for the prevention of relapse in schizophrenia – Johnson & Johnson
Johnson & Johnson announced that the FDA has approved a supplemental New Drug Application (sNDA) based on long-term data evaluating the safety and efficacy of Caplyta (lumateperone) for the prevention of relapse in schizophrenia. The data further reinforces the long-term efficacy and tolerability of Caplyta as the latest addition to Johnson & Johnson’s leading portfolio of neuropsychiatric therapies.
Relapse is one of the most consequential challenges for people living with schizophrenia—disrupting stability, undermining functioning, and often triggering episodes of psychosis, hallucinations, and other symptoms that can derail daily life for patients and their loved ones. Schizophrenia is a complex, chronic, and progressive condition affecting approximately 2.8 million adults in the United States, yet it remains significantly undertreated, with roughly 40 percent of individuals not receiving adequate care. On average, adults living with schizophrenia experience nine relapse episodes within a six-year period, which is why reducing relapse risk is a critical goal in long-term management, and can help preserve functioning, reduce caregiver and societal strain, and break the cycle of repeated hospitalization. Reducing relapse also mitigates the substantial economic burden associated with the disease, as the societal cost of schizophrenia in 2024 was estimated at $366.8 billion in the U.S.
In the Phase III, double-blind, randomized withdrawal trial supporting this update, Caplyta significantly extended time to relapse versus placebo during the 26-week double-blind treatment period (p=0.0002), helping support long-term stability for adults living with schizophrenia. Patients who received Caplyta had a 63 percent lower risk of relapse compared with placebo (hazard ratio = 0.37), and 84 percent of patients were relapse-free over six months. Caplyta also significantly delayed time to all-cause treatment discontinuation, including relapse. The 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 percent of patients and at least twice the rate of placebo.
“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, M.D., Clinical Professor of Psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York.a “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.”
While its exact mechanism of action is unknown, Caplyta 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 similar to placebo in weight change, metabolic effects, and extrapyramidal symptoms, which are often cited as reasons for treatment discontinuation. In the Phase III, 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 patients treated with Caplyta experienced a mean weight change of –2.05 kg (–4.52 lbs.) over one year, with sustained improvements or stability in metabolic parameters. Caplyta makes it easy to start and stay on treatment without the need for titration.
“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, Vice President Global Medical Affairs, Neuroscience, Innovative Medicine, Johnson & Johnson. “This label update—backed by long-term Phase III 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 FDA approved in adults as an adjunctive therapy with antidepressants for major depressive disorder (MDD), schizophrenia, and depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy, and as adjunctive therapy with lithium or valproate. This label update builds upon the existing clinical data and postmarketing experience across its approved uses. Caplyta is also being evaluated in clinical studies for other neuropsychiatric and neurological conditions beyond its current FDA-approved indications.
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 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=110) or switch 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.
