Positive new results have emerged from the Intra-Cellular Therapies 502 study, evaluating lumateperone (Caplyta) 42 mg as an adjunct therapy to antidepressants for treating major depressive disorder (MDD). Lumateperone 42 mg achieved significant and clinically meaningful outcomes in both primary and key secondary endpoints1.
This study, along with the positive phase 3 trial (study 501), forms the basis for lumateperone’s supplemental New Drug Application (sNDA) for adjunctive MDD treatment. The sNDA will be submitted to the FDA in the second half of 20242.
“We are confident that the efficacy results from studies 501 and 502, along with the favorable safety and tolerability profiles, will position lumateperone as the preferred drug for MDD patients who have an inadequate response to antidepressants,” said Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies. “We are very pleased with the strong efficacy results from study 502, which align with the compelling results from study 501. These results further support our vision for Caplyta to become a leading option for patients and providers dealing with depression.”
Approximately 480 patients were randomized into two groups to receive lumateperone 42 mg plus an antidepressant or a placebo plus an antidepressant, to evaluate lumateperone’s efficacy and safety as an adjunct treatment in MDD patients. The 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 showing a statistically significant and clinically meaningful reduction in MADRS total score compared to placebo at week 6. In the modified intention-to-treat 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 and statistically significant separation began at week 2, continuing throughout the study.
Lumateperone 42 mg also met the primary secondary endpoint by showing 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 significant difference in CGI-S compared to placebo was observed starting at week 3 and continued throughout the study.
In study 502, lumateperone 42 mg significantly 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 assessing nine 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, similar to previous studies of lumateperone as a treatment for MDD, bipolar depression, and schizophrenia.
“MDD is the leading cause of disability globally, with about two-thirds of patients failing 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 studies, 501 and 502, lumateperone showed a strong effect as an adjunct treatment to antidepressants in MDD patients with an inadequate response. The consistent efficacy, safety, and tolerability of lumateperone make it a promising treatment option for MDD.”
To read more about lumateperone, refer to the poster presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting, discussing a recent clinical trial on lumateperone’s efficacy for treating depressive symptoms in MDD or bipolar depression patients with mixed features3.
References
Footnotes
- https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-positive-topline-results-1 ↩
- https://www.psychiatrictimes.com/view/new-phase-3-study-results-on-lumateperone-an-adjunctive-therapy-to-antidepressants ↩
- https://www.psychiatrictimes.com/view/evaluating-the-efficacy-of-lumateperone-for-MDD-and-bipolar-depression-with-mixed-features ↩