Lumateperone as adjunct significantly reduces depression symptoms in patients with major depressive disorder phase 3 trial shows

This trial, in conjunction with our previously reported positive Phase 3 study, Study 501, forms the basis for our lumateperone sNDA for the adjunctive treatment of MDD. We expect to submit this sNDA to the U.S. Food and Drug Administration (FDA) in the second half of 2024.

“We are confident that the efficacy results from Studies 501 and 502, along with the favorable safety and tolerability profiles from these studies, will make lumateperone a drug of choice for patients suffering with MDD who are having an inadequate response to antidepressant therapy,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “We are very pleased with the robust efficacy results from Study 502 which are consistent with the compelling results from Study 501. These results, further support our vision for CAPLYTA to become a leading option for patients and providers across mood disorders.”

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.

In this study, 480 patients were randomized (1:1) to lumateperone 42 mg plus antidepressant or placebo plus antidepressant to evaluate the efficacy and safety of lumateperone as an adjunctive treatment to antidepressants in patients with MDD. The baseline MADRS total score was 30.8 for lumateperone 42 mg and 31.5 for placebo.

“MDD is the leading cause of disability in the world, where about two-thirds of patients fail to achieve remission with first-line treatment,” said Dr. Suresh Durgam, Executive Vice President, Chief Medical Officer of Intra-Cellular Therapies. “In both pivotal registrational studies, Study 501 and Study 502, lumateperone demonstrated a robust effect as an adjunctive treatment to antidepressants in patients with MDD who had inadequate response to antidepressant therapy. The consistent efficacy, safety and tolerability profile of lumateperone has the potential to be a compelling treatment option for MDD.”

About the Lumateperone Adjunctive MDD Program

Studies 501 and 502 evaluated lumateperone 42 mg as an adjunctive treatment to antidepressants in patients with MDD who had inadequate response to antidepressant therapy.

These are both multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose studies conducted globally in patients with a primary diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who have had an inadequate response to ongoing anti-depressant therapy.

Eligible patients had a minimum MADRS total score of 24, a minimum CGI-S score of 4 and an inadequate response to one or two SSRI/SNRIs (less than 50% improvement) following monotherapy treatment for at least 6 weeks duration.

The primary endpoint results from Studies 501 and 502 are as follows:

In the pooled safety data of Studies 501 and 502, the most common adverse events (≥5% and greater than twice placebo) with lumateperone versus placebo were: dizziness (16.6% v. 5.0%), dry mouth (12.6% v. 3.3%), somnolence (12.2% v. 2.3%), nausea (8.5% v. 4.0%) and fatigue (7.2% v. 1.2%).

About Major Depressive Disorder

Major Depressive Disorder (MDD) is a common mood disorder in the U.S. affecting an estimated 21 million adults each year. MDD represents the primary cause of disability in the world. Symptoms include sadness, hopelessness, helplessness, feelings of guilt, irritability, loss of interest in formerly pleasurable activities, cognitive impairment, disturbed sleep patterns, and suicide ideation or behavior. It can cause severe functional impairment, adversely affecting interpersonal relationships, and may impact quality of life. Approximately two-thirds of patients with depression fail to achieve remission with first-line treatment.