New Phase 3 Data Analysis: Lumateperone Shows Promise for Remission of Major Depressive Disorder

Johnson & Johnson has announced a new analysis of phase 3 data which found lumateperone (Caplyta), in combination with an antidepressant, showed significantly greater remission rates in adults with major depressive disorder (MDD) than placebo plus an antidepressant at 6 weeks, with continued benefits observed through 6 months in an open-label extension study. These findings were presented at the American College of Neuropsychopharmacology 64th Annual Meeting on January 12-15 in the Bahamas.¹

To evaluate how Caplyta may help patients achieve the goal of remission, the analysis draws from 3 phase 3 studies of Caplyta, including pooled data from 2 pivotal efficacy and safety trials (studies 501 and 502) and a 6-month open-label extension safety study (study 503). The analysis evaluated 3 measures of remission to assess the potential resolution and durability of relief from symptoms, as defined by the Montgomery-Asberg Depression Rating Scale (MADRS): remission (defined as MADRS ≤10), complete remission (defined as MADRS ≤5), and sustained remission (defined as MADRS ≤10 maintained at each assessment). Across all 3 measures, participants taking Caplyta saw meaningful remission rates. This highlights both the depth and durability of improvement for patients living with MDD.

“Today, remission is out of reach for the majority of patients with depression, which means they continue to struggle with persistent symptoms that negatively impact their daily lives,” said Michael E. Thase, MD, a professor of psychiatry and chief of the Division of Mood and Anxiety Disorders Treatment & Research Program at the Perelman School of Medicine at University of Pennsylvania. “These data capture not only symptom reduction, but also the durability and depth of treatment response, which are critical benchmarks for patients and clinicians striving for lasting relief. The findings demonstrate that adjunctive lumateperone may almost double the likelihood of remission, with benefits sustained over 6 months, offering renewed hope to millions of adults seeking recovery from this disease.”

In the pooled pivotal data, nearly double the number of participants reached remission (MADRS ≤10) at 6 weeks with adjunctive Caplyta compared with placebo (25.5% vs 13.6%; nominal P<0.0001), with 10.6% of participants achieving complete remission (MADRS ≤5) with Caplyta plus an antidepressant compared with 5.6% with placebo plus an antidepressant (P<0.01). At 6 weeks, significantly greater remission rates with Caplyta vs placebo were consistent across patient subgroups, including age, antidepressant type (SSRI/SNRI), and baseline severity.

In study 503, which was a 6-month open-label extension safety study (n = 809), efficacy was maintained with long-term Caplyta treatment, with nearly 2 out of 3 participants (65.4%; n = 529) reaching remission (MADRS ≤10). Complete remission (MADRS ≤5) was reached by 44.1% (n = 357) of participants. Notably, 42.8% (n = 346) of participants experienced sustained remission (MADRS ≤10 at each assessment) by the end of treatment, with rates increasing steadily throughout the study: week 8 (28.6%; n = 231), week 16 (37.2%; n = 301), and week 24 (40.8%; n = 330). Again, remission rates were consistent across patient subgroups, including age, antidepressant type (SSRI/SNRI), and baseline severity.

“What matters most to patients isn’t just an improvement in symptoms, but sustained relief that allows them to truly reclaim their lives,” said Bill Martin, PhD, the global therapeutic area head of neuroscience at Johnson & Johnson Innovative Medicine. “Too many patients spend years cycling through treatments, settling for ‘good enough’ because they don’t realize complete relief is possible. These data demonstrate that remission is within reach and should be the expectation, not the exception.”

Just back in November 2025, Caplyta was approved by the US Food and Drug Association (FDA) as an adjunctive therapy for MDD and is also indicated for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder.² Caplyta’s mechanism of action is unknown; however, investigators do know that Caplyta is characterized by high serotonin 5-HT2A receptor occupancy and moderate amounts of dopamine D2 receptor occupancy at therapeutic doses. Caplyta does not require dose titration, which allows patients to start treatment at the effective dose of 42 mg.

Additionally, in July 2025, a supplemental New Drug Application (sNDA) for Caplyta with long-term data evaluating the safety and efficacy of the medication for the prevention of relapse in schizophrenia was submitted to the FDA.³ This sNDA submission is based upon positive results from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal trial.

References

1. New clinical data highlights CAPLYTA® (lumateperone) as a promising option for achieving remission in adults with major depressive disorder. News release. January 16, 2026. Accessed January 16, 2026. https://www.jnj.com/media-center/press-releases/new-clinical-data-highlights-caplyta-lumateperone-as-a-promising-option-for-achieving-remission-in-adults-with-major-depressive-disorder

2. Kuntz L. FDA approves Caplyta for adjunctive treatment of major depressive disorder. Psychiatric Times. November 6, 2025. https://www.psychiatrictimes.com/view/fda-approves-caplyta-for-adjunctive-treatment-of-major-depressive-disorder

3. Kuntz L. sNDA submitted: lumateperone for the prevention of relapse in schizophrenia. Psychiatric Times. July 8, 2025. https://www.psychiatrictimes.com/view/snda-submitted-lumateperone-for-the-prevention-of-relapse-in-schizophrenia