Lumateperone as an Adjunctive Therapy to Antidepressants: More Positive Results

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There are new positive topline results from Intra-Cellular Therapies’ study 502 evaluating lumateperone (Caplyta) 42 mg as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). Lumateperone 42 mg achieved statistically significant and clinically meaningful results in both the primary and the key secondary endpoints.¹

This study—as well as the positive phase 3 trial, study 501²—forms the basis for the lumateperone sNDA for the adjunctive treatment of MDD. The sNDA will be submitted to the US Food and Drug Administration (FDA) in the latter 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 Sharon Mates, PhD, 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.”

Approximately 480 patients were randomized 1:1 to receive 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 Montgomery-Åsberg Depression Rating (MADRS) total score was 30.8 for lumateperone 42 mg and 31.5 for placebo.

Lumateperone 42 mg met the primary endpoint 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 study population, the least squares (LS) mean reduction from baseline for lumateperone 42 mg was 14.7 points, vs 10.2 points for placebo (LS mean difference = -4.5 points; P <0.0001). Improvement over placebo on the MADRS total score was seen as early as week 1 (P=0.0504) and statistically significant separation started at week 2 and was maintained throughout the study.

Lumateperone 42 mg also met the key secondary endpoint by demonstrating a statistically significant and clinically meaningful reduction in the Clinical Global Impression Scale for Severity of Illness (CGI-S) score compared to placebo at week 6 (P <0.0001). Statistically significant separation on the CGI-S compared with placebo was observed starting at week 3 and maintained throughout the study.

In study 502, lumateperone 42 mg robustly improved depressive symptoms as reported by patients as measured by the Quick Inventory of Depressive Symptomatology Self Report (P <0.0001), a 16-item patient-rated scale of symptom severity in depression that assesses 9 key symptoms.

Lumateperone was generally safe and well-tolerated, with the most common adverse events (≥5% and greater than twice placebo) being dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue. Adverse events were mostly mild to moderate resolved during the study, and generally similar to those seen in former studies of lumateperone as a treatment for MDD, bipolar depression, and schizophrenia.

“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 Suresh Durgam, MD, executive vice president and 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.”

To read more on lumateperone, check out this poster at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which discussed the results of a recent clinical trial exploring the efficacy of lumateperone for the treatment of depressive symptoms in patients with either MDD or bipolar depression with mixed features. Investigators determined that lumateperone 42 mg is a promising treatment for patients with depressive episodes with mixed features in MDD or bipolar disorder.³

References

1. Intra-Cellular Therapies announces positive topline results in second phase 3 trial evaluating lumateperone as adjunctive therapy in patients with major depressive disorder. News release. June 18, 2024. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-positive-topline-results-1

2. Kuntz L. New phase 3 study results on lumateperone, an adjunctive therapy to antidepressants. Psychiatric Times. April 16, 2024. https://www.psychiatrictimes.com/view/new-phase-3-study-results-on-lumateperone-an-adjunctive-therapy-to-antidepressants

3. O’Brien E. Evaluating the efficacy of lumateperone for MDD and bipolar depression with mixed features. Psychiatric Times. May 30, 2024. https://www.psychiatrictimes.com/view/evaluating-the-efficacy-of-lumateperone-for-mdd-and-bipolar-depression-with-mixed-features