J&J Submits sNDA to FDA for Lumateperone (CAPLYTA) to Prevent Schizophrenia Relapse

On July 8, 2025, Johnson & Johnson announced that the company submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for lumateperone (CAPLYTA) to prevent schizophrenia relapse.

The sNDA submission was based on long-term phase 3 data showing that lumateperone led to a 63% reduction in the risk of relapse in adults with schizophrenia compared to placebo. Lumateperone 42 mg, an oral, once-daily atypical antipsychotic, is characterized by high serotonin 5-HT2A receptor occupancy and lower amounts of dopamine D2 receptor occupancy at therapeutic doses.

“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, in a statement. “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.”

Lumateperone is FDA-approved to treat schizophrenia as a monotherapy or an adjunctive therapy with lithium or valproate. The drug is also already approved for bipolar disorder (I and II) and depression as an adjunctive and monotherapy. An NDA for lumateperone as an adjunctive major depressive disorder (MDD) is currently under FDA review.

Lumateperone may already be approved to treat schizophrenia, but the data support the drug’s safety and efficacy in preventing schizophrenia relapse.

The phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal 47-week trial included an 18-week open-label and 26-week double-blind phase. During the open-label phase, patients with schizophrenia were treated with lumateperone 42 mg per day. Patients who met the stabilization criteria during the open-label period entered the double-blind phase, where they were randomized to either continue lumateperone 42 mg (n = 114) or switch to placebo (n = 114) for 26 weeks or until relapse.

The phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal trial showed that time to relapse during the 26-week double-blind treatment phase was significantly longer in patients on lumateperone vs placebo (P = .0002). Additionally, compared with placebo, lumateperone was linked to a 63% reduction in the risk of relapse (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22 – 0.65).

The study also showed significantly delayed time to all-cause discontinuation among patients on lumateperone vs placebo during the double-blind phase (P = .0007). Lumateperone had a consistent safety profile in earlier clinical trials, with similar rates of weight change, metabolic effects, and extrapyramidal symptoms; no new safety concerns were identified. Common adverse events included a headache, somnolence/sedation, dizziness, nausea, and dry mouth.

“Relapse prevention is a critical goal for the long-term care and management of this debilitating disorder,” said Bill Martin, PhD, Global Therapeutic Area Head, Neuroscience, at Johnson & Johnson Innovative Medicine, in a statement. “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.”

References

Supplemental new drug application submitted to U.S. FDA for CAPLYTA® (lumateperone) with data demonstrating significant schizophrenia relapse prevention compared to placebo. Johnson & Johnson. July 8, 2025. https://www.jnj.com/media-center/press-releases/supplemental-new-drug-application-submitted-to-u-s-fda-for-caplyta-lumateperone-with-data-demonstrating-significant-schizophrenia-relapse-prevention-compared-to-placebo. Accessed July 9, 2025.