Intra-Cellular Therapies Reports Positive Phase 3 Results for Lumateperone as Adjunctive MDD Therapy

Intra-Cellular Therapies, Inc. has announced promising results from their Study 502, which assessed lumateperone 42 mg used as an adjunctive treatment to antidepressants for Major Depressive Disorder (MDD). This study, alongside the previously successful Phase 3 Study 501, builds the foundation for their supplemental New Drug Application (sNDA) for lumateperone as an adjunctive MDD therapy, which they plan to submit to the FDA in the latter half of 2024.

Dr. Sharon Mates, CEO of Intra-Cellular Therapies, expressed confidence in lumateperone based on the consistent and robust results from both studies, suggesting that lumateperone could become a preferred option for MDD patients who have not responded adequately to traditional antidepressant treatments.

Study 502's primary endpoint was the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline at Week 6. Lumateperone 42 mg demonstrated a statistically significant and clinically meaningful reduction in the MADRS score compared to placebo. Specifically, the least squares mean reduction from baseline for lumateperone was 14.7 points versus 10.2 points for placebo, with a mean difference of -4.5 points (p<0.0001). This numerical improvement was noted as early as Week 1 and remained significant throughout the study.

The key secondary endpoint focused on the Clinical Global Impression Scale for Severity of Illness (CGI-S), where lumateperone also showed significant improvement compared to placebo at Week 6 (p<0.0001). The statistical separation from placebo on the CGI-S was observed starting at Week 3 and remained throughout the study.

Additionally, lumateperone significantly improved patient-reported depressive symptoms as measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR-16) scale (p<0.0001). The QIDS-SR-16 evaluates the severity of depression symptoms, including sleep issues, mood, appetite, self-perception, concentration, interest in activities, suicidal thoughts, psychomotor agitation, and fatigue.

Safety and tolerability were consistent with previous lumateperone trials, showing that the drug was generally well-tolerated. The most common adverse events (≥5% and greater than twice the placebo incidence) were dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue, mostly mild to moderate and resolving during the study.

In Study 502, 480 patients were randomized to receive either lumateperone 42 mg with an antidepressant or a placebo with an antidepressant. The baseline MADRS total scores were 30.8 for the lumateperone group and 31.5 for the placebo group. Dr. Suresh Durgam, Executive Vice President and Chief Medical Officer, noted that MDD is a leading cause of disability globally, with many patients not achieving remission with first-line treatments. He emphasized that the consistent efficacy, safety, and tolerability of lumateperone offer a promising new treatment option for MDD patients.

Both Studies 501 and 502 were multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose studies conducted globally. They included patients diagnosed with MDD according to DSM-5 criteria who had an inadequate response to one or two SSRIs/SNRIs after at least six weeks of treatment.

In summary, lumateperone 42 mg has shown significant promise as an adjunctive treatment for MDD, demonstrating substantial efficacy and a favorable safety profile. This bodes well for its potential approval by the FDA and subsequent use in clinical practice to address the unmet needs of MDD patients resistant to initial therapies.