Intra-Cellular Therapies has announced positive results from a phase 3 study evaluating the efficacy and safety of lumateperone (Caplyta) 42 mg for preventing symptomatic relapse in adults with schizophrenia. The multicenter, randomized, double-blind, placebo-controlled trial demonstrated a significant delay in time to relapse for patients treated with lumateperone compared to those receiving placebo.
The 47-week study (Study 304) included an 18-week open-label phase where participants received 42 mg of lumateperone daily. Those who met stabilization criteria were then enrolled in a 26-week double-blind treatment phase, randomized to either continue lumateperone or switch to placebo (n=114 per group). The primary endpoint was time to relapse, with a key secondary endpoint being time to all-cause discontinuation.
Efficacy and Safety Results
The results indicated a significantly longer time to relapse in the lumateperone group compared to placebo (P = .0002), with 18 and 44 relapses, respectively. Treatment with lumateperone was associated with a 63% reduction in the risk of relapse compared to placebo (HR, 0.37; 95% CI, 0.22-0.65). The drug was also generally safe and well-tolerated during the study.
Suresh Durgam, Executive Vice President and Chief Medical Officer of Intra-Cellular Therapies, noted that controlling symptoms and preventing relapses is critical for improving long-term patient outcomes in schizophrenia, a chronic and severe neurological condition affecting an estimated 1.1% of the US population (2.8 million adults).
Current Schizophrenia Treatment Landscape
Schizophrenia is characterized by acute psychotic episodes that can worsen disease prognosis over time. While there is no cure, available treatments have comparable success rates to those for heart disease. However, adherence to treatment is crucial, as approximately 80% of individuals who discontinue medication after an acute episode will experience relapse within one year, compared to 30% of those who continue treatment.
Lumateperone was initially approved by the FDA for the treatment of schizophrenia in adults in December 2019, based on efficacy demonstrated in two placebo-controlled trials. It also received FDA approval in December 2021 for the treatment of bipolar depression as either monotherapy or adjunctive therapy with lithium or valproate.
Important Safety Information
Lumateperone carries boxed warnings regarding increased risk of death in elderly patients with dementia-related psychosis and the need to monitor patients on antidepressants for clinical worsening and suicidal thoughts/behaviors. The drug is not approved for dementia-related psychosis.
Other warnings include the potential for cerebrovascular adverse events (including stroke and transient ischemic attack) in older patients with dementia-related psychosis, neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, leukopenia, neutropenia, agranulocytosis, decreased blood pressure, dizziness, falls, and seizures. Lumateperone should not be used with CYP3A4 inducers, and dose reduction is recommended when used with strong or moderate CYP3A4 inhibitors.
