Lumateperone Demonstrates Efficacy in Reducing Symptomatic Relapse Risk in Schizophrenia

Intra-Cellular Therapies has announced positive results from a study evaluating safety and efficacy of 42 mg lumateperone (Caplyta) for symptomatic relapse prevention in adults with schizophrenia, according to a company news release.¹

Lumateperone is also approved to treat bipolar depression. | Image credit: Feng Yu

Study 304 is a multicenter, randomized, double-blind, placebo-controlled, parallel group study of lumateperone. The 47-week study included an 18-week open-label phase; participants who met stabilization criteria with 42 mg daily lumateperone therapy were enrolled in the double-blind treatment phase. The primary study endpoint was time to relapse; key secondary endpoints included time to all-cause discontinuation. Both endpoints were measured during the double-blind treatment phase.

Participants who progressed to the double-blind treatment phase were randomly assigned to either continue on lumateperone therapy or to switch to placebo (n=114 each) for up to 26 weeks or until relapse occurred.

Time to relapse was significantly longer in the treatment group vs placebo (P =.0002), with 18 and 44 relapses in the lumateperone and placebo groups, respectively. Treatment was also associated with a 63% risk reduction of relapse vs placebo (HR, 0.37; 95% CI, 0.22-0.65). Lumateperone was also generally safe and well tolerated.

READ MORE: Schizophrenia Drug Approved by FDA Represents First New Treatment Option in Decades

Lumateperone was initially approved by the FDA for the treatment of schizophrenia in adults in December 2019,² with efficacy demonstrated in 2 placebo-controlled trials. The drug also received FDA approval in December 2021 to treat bipolar depression as either monotherapy or adjunctive therapy with lithium or valproate.³

“Schizophrenia is a chronic, serious mental illness characterized by the occurrence of acute psychotic episodes that cumulatively worsen disease prognosis. The control of symptoms and the prevention of relapses is critical to improving long-term patient outcomes, said Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies.

Lumateperone includes 2 boxed warnings. Older adults with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death; lumateperone is not approved for the treatment of patients with dementia-related psychosis. Patients being treated with antidepressants should be closely monitored for both clinical worsening and the emergency of suicidal thoughts or behaviors.

Antipsychotic drugs may cause cerebrovascular adverse events, including stroke and transient ischemic attack, in older patients with dementia-related psychosis. Neuroleptic malignant syndrome is also possible, as is tardive dyskinesia, metabolic changes, leukopenia, neutropenia, and agranulocytosis, decreased blood pressure and dizziness, falls, and seizures, among other adverse events.

READ MORE: The Psychedelic Pharmacy: A Paradigm Shift in Mental Health Treatment

Additionally, lumateperone should not be used with CYP3A4 inducers; dose reduction is recommended when used with strong or moderate CYP3A4 inhibitors.

Schizophrenia is a chronic, severe neurological condition estimated to affect 1.1% of the US population, or 2.8 million US adults. Estimates suggest that 40% of adults with schizophrenia are “untreated in any given year,” according to the Treatment Advocacy Center. Although there is no cure for schizophrenia, available treatments have a comparable treatment success rate to those for heart disease. However, continued treatment is critical: approximately 80% of individuals who discontinue their medications after an acute episode will experience relapse within 1 year, compared with 30% of those who continue treatment.⁴

READ MORE: Mental and Behavioral Health Resource Center

References

1. Intra-Cellular Therapies announces positive topline results in phase 3 trial evaluating Caplyta for the prevention of relapse in patients with schizophrenia. News release. Intra-Cellular Therapies. November 5, 2024. Accessed November 5, 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

2. FDA approves Intra-Cellular Therapies’ novel antipsychotic, Caplyta (lumateperone) for the treatment of schizophrenia in adults. News release. Intra-Cellular Therapies. December 23, 2019. Accessed November 5, 2024. https://ir.intracellulartherapies.com/news-releases/news-release-details/fda-approves-intra-cellular-therapies-novel-antipsychotic

3. Intra-Cellular Therapies announces US FDA approval of Caplyta (lumateperone) for the treatment of bipolar depression in adults. News release. Intra-Cellular Therapies. December 20, 2021. Accessed November 5, 2024. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-us-fda-approval-caplytar

4. Schizophrenia fact sheet. Treatment Advocacy Center. Accessed November 5, 2024. https://www.tac.org/reports_publications/schizophrenia-fact-sheet