Lumateperone effective in schizophrenia

Lumateperone has demonstrated efficacy in improving symptoms of schizophrenia as well as a favourable safety profile in a recent phase III study.

“The unique pharmacologic mechanisms of lumateperone seem to confer antipsychotic efficacy with favourable safety and tolerability,” said the researchers. “The efficacy and safety profiles of lumateperone may differ in important ways from existing treatments for patients with schizophrenia.” [JAMA Psychiatry 2020, doi: 10.1001/jamapsychiatry.2019.4379]

Among 450 adult patients with schizophrenia experiencing an acute exacerbation of psychosis, lumateperone 42 mg demonstrated a statistically significant improvement in Positive and Negative Syndrome Scale (PANSS) total score from baseline to day 28 vs placebo (least-squares mean difference [LSMD], -4.2; 95 percent confidence interval [CI], -7.8 to -0.6; unadjusted p=0.02). The statistically significant differences in PANSS total score were observed from day 8 to day 28 of assessment.

Treatment with lumateperone 42 mg and 28 mg demonstrated statistically significant improvements in Clinical Global Impression-Severity (CGI-S) central score from baseline to day 28 compared with placebo (42 mg: LSMD, -0.3; 95 percent CI, -0.5 to -0.1; p=0.003; 28 mg: LSMD, -0.2; 95 percent CI, -0.5 to 0.0; unadjusted p=0.02).

PANSS positive subscale score was improved with lumateperone 42 mg and 28 mg from baseline to day 28 compared with placebo (42 mg: LSMD, -1.7; 95 percent CI, -2.9 to -0.5; p=0.006; 28 mg: LSMD, -1.2; 95 percent CI, -2.4 to -0.1; p=0.04). There was, however, no significant improvement in PANSS negative subscale score with treatment.

In this randomized, double-blind, placebo-controlled, phase III clinical trial, 450 patients aged 18–60 years (mean, 42.4 years) with schizophrenia experiencing an acute exacerbation of psychosis were enrolled from 12 clinical trials in the US. Patients (male, 77.1 percent; mean baseline PANSS score, 89.8; mean baseline CGI-S score, 4.8) were randomized 1:1:1 (150 patients in each arm) to receive lumateperone 42 mg, lumateperone 28 mg, or placebo.

Lumateperone is the active free base form of the oral drug, lumateperone tosylate. In the trial, both lumateperone doses were well tolerated without clinically significant treatment-emergent adverse motor adverse effects or changes in cardio-metabolic or endocrine factors vs placebo. Somnolence was the most common adverse event in any treatment arm (42 mg: 17.3 percent; 28 mg: 11.3 percent; placebo: 4.0 percent).