The Efficacy of Lumateperone 42 mg in the Treatment of Schizophrenia: A Pooled Analysis of Randomized Controlled Trials

Introduction: Lumateperone (lumateperone tosylate, ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate. This pooled analysis of 2 double-blind, placebo-controlled studies evaluated the efficacy of lumateperone 42mg in the treatment of patients with acute exacerbation of schizophrenia.

Methods: Data were pooled from 2 controlled late-phase studies. The primary efficacy endpoint was change from baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total score. Secondary assessments included change from baseline in PANSS subscale scores and Clinical Global Impressions–Severity (CGI-S) score. Additional secondary endpoints were percent of patients meeting various PANSS response criteria (20%, 30%, and 40% improvement).

Results: The intent-to-treat population comprised 520 patients (221, placebo; 224, lumateperone 42mg; 75, risperidone 4mg). Lumateperone 42mg significantly reduced PANSS Total score compared with placebo (least squares mean difference versus placebo [LSMD]=−4.76; P < .001) with efficacy similar to risperidone 4mg (LSMD=−4.97; P=.014). Lumateperone 42mg also showed significant efficacy vs placebo across 2 PANSS subscales analyzed: Positive Subscale (LSMD=−1.71, P < .001) and General Psychopathology Subscale (LSMD=−2.04, P=.009), and on the CGI-S (LSMD=−0.29, P < .001). Lumateperone 42mg was associated with significantly higher PANSS response rates than placebo for each criterion level.

Conclusions: In this pooled analysis, lumateperone 42mg significantly improved the symptoms of schizophrenia. Improvement on various PANSS subscales and greater rates of PANSS response suggest that lumateperone 42mg has broad efficacy across schizophrenia symptoms and is associated with clinically meaningful improvement.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.