sNDA Submitted: Lumateperone for the Prevention of Relapse in Schizophrenia

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Johnson & Johnson today announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) based upon long-term data evaluating the safety and efficacy of lumateperone (Caplyta) for the prevention of relapse in schizophrenia.¹

Caplyta 42 mg is an oral, once daily atypical antipsychotic approved for the treatment of adults with schizophrenia and depressive episodes associated with bipolar depression, as both monotherapy and as adjunctive therapy with lithium or valproate.

“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, MD, clinical professor of Psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York. “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 sNDA submission is based upon positive results from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal trial. Investigators found time to relapse during the 26-week double-blind treatment phase was significantly longer in patients receiving Caplyta compared with those receiving placebo (P=0.0002), the primary endpoint of the study. Treatment with Caplyta was also associated with a 63% reduction in risk of relapse vs placebo (hazard ratio [95% CI] = 0.37, [0.22, 0.65]). Investigators also found a significantly delayed time to all-cause discontinuation, including relapse, compared with placebo during the double-blind phase (P=0.0007), the key secondary endpoint. Caplyta’s safety profile was consistent with the existing body of clinical data. 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.

“Relapse prevention is a critical goal for the long-term care and management of this debilitating disorder,” said Bill Martin, PhD, the global therapeutic area head of neuroscience at 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 are 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.”

Although Caplyta’s exact mechanism of action is unknown, it 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 comparable with placebo in terms of weight change, metabolic effects, and extrapyramidal symptoms. The most commonly reported adverse events were somnolence/sedation, dizziness, nausea, and dry mouth.

An sNDA for Caplyta as an adjunctive treatment for adults with major depressive disorder (MDD) is also currently under FDA review, submitted back in December 2024.² This sNDA is based upon data from studies 501 and 502, which are 2 positive phase 3 global, double-blind, placebo-controlled studies in participants with a primary diagnosis of MDD who have had an inadequate response to antidepressants.Caplyta, when added to antidepressant treatment, demonstrated robust efficacy for MDD in the primary endpoint, the Montgomery Asberg Depression Rating Scale (MADRS) total score, with a large separation vs placebo of 4.9 points (effect size 0.61) in study 501 and 4.5 points (effect size 0.56) vs placebo in study 502.

References

1. Supplemental new drug application submitted to U.S. FDA for CAPLYTA® (lumateperone) with data demonstrating significant schizophrenia relapse prevention compared to placebo. News release. July 8, 2025. https://www.investor.jnj.com/news/news-details/2025/Supplemental-new-drug-application-submitted-to-U-S--FDA-for-CAPLYTA-lumateperone-with-data-demonstrating-significant-schizophrenia-relapse-prevention-compared-to-placebo/default.aspx

2. Kuntz L. sNDA submitted: lumateperone as adjunctive therapy for major depressive disorder. Psychiatric Times. December 3, 2024. https://www.psychiatrictimes.com/view/snda-submitted-lumateperone-as-adjunctive-therapy-for-major-depressive-disorder