Lumateperone as an adjunctive therapy to antidepressants: More positive results

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

This study—as well as the positive phase 3 trial, study 501²— forms the basis for lumateperone sNDA for the adjunctive treatment of MDD. The sNDA will be submitted to the US Food and Drug Administration (FDA) in the second half of 2024.

“We are confident that the efficacy results from studies 501 and 502, together with the favorable safety and tolerability profiles from these studies, will make lumateperone the drug of choice for patients suffering from MDD who have an inadequate response to therapy.” antidepressants,” he said. Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies. “We are very pleased with the strong 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 of humor.”

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 add-on treatment to antidepressants in patients with MDD. The total baseline Montgomery-Åsberg Depression Rating Score (MADRS) 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 MADRS total score compared to placebo at week 6. In the modified intention-to-treat 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). Improvement over placebo in MADRS total score was seen as early as week 1 (P=0.0504) and statistically significant separation began at week 2 and was maintained throughout the study.

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

In study 502, lumateperone 42 mg strongly improved patient-reported depressive symptoms as measured by the Rapid Self-Report Depressive Symptom Inventory (P <0.0001), a 16-item patient-rated depressive symptom severity scale that assesses 9 core symptoms.

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

“MDD is the leading cause of disability in the world, with approximately two-thirds of patients failing to achieve remission with first-line treatment,” said Suresh Durgam, MD, executive vice president and chief medical officer of Cellular Therapies. “In both pivotal registration studies, study 501 and study 502, lumateperone showed a strong effect as an add-on treatment to antidepressants in patients with MDD who had an 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 about lumateperone, see this poster at the American Society of Clinical Psychopharmacology (ASCP) 2024 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 MDD or bipolar depression with mixed features. The 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. Intracellular therapies announce positive 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. Results of the new phase 3 study of 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. 30 May 2024. https://www.psychiatrictimes.com/view/evaluating-the-efficacy-of-lumateperone-for-mdd-and-bipolar-depression-with-mixed-features