Lumateperone (ITI-007) for the Treatment of Schizophrenia: Overview of Placebo-Controlled Clinical Trials and an Open-label Safety Switching Study

Background: Lumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems.

Methods: The lumateperone clinical program in schizophrenia includes 3 controlled clinical trials (Study 005, n=335; Study 301, n=450; and Study 302, n=696) to evaluate efficacy. The primary endpoint was change in PANSS total score compared to placebo.  Also, an open-label safety switching study was conducted in which 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6 weeks with lumateperone and then switched back to SOC.

Results: In Studies 005 and 301, 60 mg ITI-007 met the primary endpoint with statistically significant superior efficacy over placebo at Day 28. In Study 302, neither dose of lumateperone separated from placebo on the primary endpoint; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and same magnitude of improvement from baseline. Lumateperone was well-tolerated with a favorable safety profile in all studies. In the two studies with risperidone included as an active control, lumateperone was statistically significantly better than risperidone on key safety and tolerability measures. In the open-label safety switching study statistically significant improvements from SOC were observed in body weight, cardiometabolic and endocrine parameters worsened again when switched back to SOC medication.

Discussion: Lumateperone represents a novel approach to the treatment of schizophrenia . The lack of cardiometabolic and motor safety issues presents a safety profile differentiated from SOC antipsychotic therapy.