Lumateperone Promising for MDD, Bipolar Depression With Mixed Features

Lumateperone monotherapy was associated with significant improvement of major depressive episodes in patients with major depressive disorder (MDD) with mixed features and in patients with bipolar depression with mixed features, according to results from a phase 3 study.

Study 403, a randomized, double-blind, placebo-controlled multicenter trial (ClinicalTrials.gov Identifier: NCT04285515), included adults with major depressive episodes associated with MDD or bipolar I or II disorder who met the DSM-5 criteria for mixed features. Patients were randomly assigned (with similar distribution between the 2 conditions) to receive either lumateperone 42mg (n=192) or placebo (n=191) once daily in the evening. 

Results showed that treatment with lumateperone met the primary endpoint demonstrating a statistically significant and clinically meaningful reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 compared with placebo:

• Combined MDD with mixed features and bipolar depression with mixed features: Least squares (LS) mean difference, -5.7; P <.0001; Cohen’s d effect size (ES)= 0.64)
• MDD with mixed features: LS mean difference, -5.9; P <.0001; ES= 0.67)
• Bipolar depression with mixed features: LS mean difference, -5.7; P <.0001; ES= 0.64)

A statistically significant and clinically meaningful reduction was also observed with lumateperone on the Clinical Global Impression of Severity Scale (CGI-S) score at week 6 compared with placebo (secondary endpoint) in the combined patient population of MDD with mixed features and bipolar depression with mixed features (P <.0001; ES= 0.59), patients with MDD with mixed features (P =.0003; ES= 0.57), and patients with bipolar depression with mixed features (P <.0001; ES= 0.61). 

The safety profile of lumateperone was consistent with that observed in previous studies. The most commonly reported adverse events were somnolence, dizziness, and nausea.

“We are very pleased with the results of this highly successful trial in these difficult to treat patient populations with mixed features in MDD and mixed features in bipolar depression,” said Dr Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “This study provides proof of concept in these patient populations and further validates lumateperone’s broad potential in mood disorders. We look forward to discussing these results with the FDA and determining next steps for the program.”

Lumateperone, an atypical antipsychotic, is currently marketed under the brand name Caplyta^® for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder.