Poster
22
(#22) Efficacy of Lumateperone 42 mg in the Treatment of Major Depressive Disorder: A Pooled Analysis of Phase 3 Randomized Controlled Trials
Psych Congress 2025
Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and bipolar depression. Lumateperone adjunctive to antidepressant therapy (ADT) demonstrated significant efficacy and was well tolerated in 2 Phase 3, randomized, double-blind, placebo-controlled studies (501/NCT04985942; 502/NCT05061706) in patients with major depressive disorder (MDD) with inadequate ADT response. This pooled analysis of Study 501 and Study 502 assessed the efficacy of lumateperone 42mg+ADT in these patients.
Method: Data were pooled from 2 studies that enrolled adults with DSM-5-defined MDD with inadequate response to 1-2 ADTs in the current depressive episode, and had Montgomery-Asberg Depression Rating Scale (MADRS) Total score≥24, Clinical Global Impression Scale-Severity (CGI-S) score≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score≥14. Primary and key secondary endpoints were changes from baseline to Day 43 in MADRS Total and CGI-S scores, respectively. Additional measures included response (≥50% MADRS decrease), remission (MADRS ≤10), and changes in QIDS-SR-16 Total score.
Results: The modified intent-to-treat population comprised 950 patients (lumateperone+ADT, n=471; placebo+ADT, n=479). At Day 43, lumateperone+ADT significantly improved MADRS Total score (least squares mean difference vs placebo [LSMD]=−4.7; effect size [ES]=−0.59; P.0001) and CGI-S score (LSMD=−0.6; ES=−0.59; P.0001) vs placebo+ADT. Lumateperone+ADT had greater MADRS response (42.9% vs 24.6%; P.0001) and remission (25.5% vs 13.6%; P.0001) rates vs placebo+ADT at Day 43. Self-reported depressive symptoms significantly improved with lumateperone+ADT at end of treatment vs placebo+ADT (QIDS-SR-16 Total score, LSMD=−2.2; ES=−0.4; P.0001).
Conclusion: Lumateperone 42mg+ADT demonstrated clinically meaningful efficacy, supporting its use as an adjunctive therapy to ADT to treat MDD in adults.
Short Description: In this pooled analysis of 2 Phase 3 studies (NCT04985942, NCT05061706) lumateperone 42mg + antidepressant therapy (ADT) demonstrated clinically meaningful efficacy in patients with major depressive disorder (MDD) with inadequate ADT response. Compared with placebo+ADT, lumateperone+ADT significantly improved Montgomery-Asberg Depression Rating Scale Total score and Clinical Global Impression Scale-Severity score, with higher response and remission rates and improved self-reported depressive symptoms. These results support lumateperone 42mg as a promising adjunctive treatment for MDD in adults.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
Method: Data were pooled from 2 studies that enrolled adults with DSM-5-defined MDD with inadequate response to 1-2 ADTs in the current depressive episode, and had Montgomery-Asberg Depression Rating Scale (MADRS) Total score≥24, Clinical Global Impression Scale-Severity (CGI-S) score≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score≥14. Primary and key secondary endpoints were changes from baseline to Day 43 in MADRS Total and CGI-S scores, respectively. Additional measures included response (≥50% MADRS decrease), remission (MADRS ≤10), and changes in QIDS-SR-16 Total score.
Results: The modified intent-to-treat population comprised 950 patients (lumateperone+ADT, n=471; placebo+ADT, n=479). At Day 43, lumateperone+ADT significantly improved MADRS Total score (least squares mean difference vs placebo [LSMD]=−4.7; effect size [ES]=−0.59; P.0001) and CGI-S score (LSMD=−0.6; ES=−0.59; P.0001) vs placebo+ADT. Lumateperone+ADT had greater MADRS response (42.9% vs 24.6%; P.0001) and remission (25.5% vs 13.6%; P.0001) rates vs placebo+ADT at Day 43. Self-reported depressive symptoms significantly improved with lumateperone+ADT at end of treatment vs placebo+ADT (QIDS-SR-16 Total score, LSMD=−2.2; ES=−0.4; P.0001).
Conclusion: Lumateperone 42mg+ADT demonstrated clinically meaningful efficacy, supporting its use as an adjunctive therapy to ADT to treat MDD in adults.
Short Description: In this pooled analysis of 2 Phase 3 studies (NCT04985942, NCT05061706) lumateperone 42mg + antidepressant therapy (ADT) demonstrated clinically meaningful efficacy in patients with major depressive disorder (MDD) with inadequate ADT response. Compared with placebo+ADT, lumateperone+ADT significantly improved Montgomery-Asberg Depression Rating Scale Total score and Clinical Global Impression Scale-Severity score, with higher response and remission rates and improved self-reported depressive symptoms. These results support lumateperone 42mg as a promising adjunctive treatment for MDD in adults.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
