In January 2025, Intra-Cellular Therapies, which was recently acquired by Johnson & Johnson in a $14.6 billion transaction, announced positive topline results from two pivotal Phase 3 trials (Studies 501 and 502) investigating Caplyta (lumateperone) 42 mg as adjunctive therapy in adults with major depressive disorder (MDD) who exhibited inadequate response to standard antidepressants. The studies enrolled over 1,200 participants and were designed to evaluate changes in depressive symptoms using the MADRS (Montgomery–Åsberg Depression Rating Scale) as the primary endpoint. Both trials demonstrated statistically significant and clinically meaningful reductions in depressive symptoms compared to placebo. Notably, improvements in core symptoms such as anhedonia, fatigue, and cognitive impairment were reported, with a favorable safety profile consistent with prior Caplyta studies. Adverse events were generally mild to moderate in severity, with low rates of akathisia and metabolic effects—key differentiators in the MDD treatment landscape. These findings further support Caplyta’s differentiated mechanism of action, which includes serotonin 5-HT2A receptor antagonism and dopamine receptor modulation, offering a novel pharmacological profile. A supplemental new drug application (sNDA) submission is anticipated by Q4 2025.

Citation: https://www.biospace.com/press-releases/intra-cellular-therapies-presents-data-from-the-caplyta-adjunctive-mdd-phase-3-program-at-the-american-college-of-neuropsychopharmacology-annual-meeting

Implications: If approved, Caplyta could become the first novel adjunctive therapy for MDD in over a decade. This development would provide clinicians with a new treatment option for patients with incomplete response to SSRIs or SNRIs, potentially improving outcomes in a large and underserved population.