Intra-Cellular Therapies, Inc. announced positive topline results from Study 502 evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD. This trial, in conjunction with previously reported positive Phase 3 study, Study 501, forms the basis for lumateperone sNDA for the adjunctive treatment of MDD. It expect to submit this sNDA to the U.S. Food and Drug Administration (FDA) in the second half of 2024.

Lumateperone 42 mg given once daily as adjunctive therapy to antidepressants met the primary endpoint in Study 502 by demonstrating a statistically significant and clinically meaningful reduction in the MADRS total score compared to placebo at Week 6. In the modified intent-to-treat (mITT) study population, the least squares (LS) mean reduction from baseline for lumateperone 42 mg was 14.7 points, versus 10.2 points for placebo (LS mean difference = -4.5 points; p<0.0001; ES= 0.56). Numerical improvement versus placebo on the MADRS total score was seen as early as Week 1 (p=0.0504) and statistically significant separation starting at Week 2 and maintained throughout the study. Lumateperone 42 mg also met the key secondary endpoint in the study by demonstrating a statistically significant and clinically meaningful reduction in the CGI-S score compared to placebo at Week 6 (p<0.0001; ES= 0.51).

Statistically significant separation on the CGI-S versus placebo was observed starting at Week 3 and maintained throughout the study. In this study, lumateperone 42 mg robustly improved depressive symptoms as reported by patients as measured by the Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR-16) (p<0.0001). The QIDS-SR-16 is a 16-item patient-rated scale of symptom severity in depression.

It assesses nine key symptoms of depression: insomnia/hypersomnia, low mood, appetite/weight changes, impaired self-perception, concentration difficulties, loss of interest/pleasure, suicidal ideation, psychomotor agitation and fatigue. Lumateperone was generally safe and well-tolerated in this study. The most common adverse events (=5% and greater than twice placebo) were dizziness, somnolence, dry mouth, nausea, diarrhea and fatigue.

Adverse events were mostly mild to moderate and resolved within the course of the study. These adverse events were generally similar to those seen in prior studies of lumateperone as a treatment for MDD, bipolar depression and schizophrenia.