New clinical data highlights Caplyta (lumateperone) as a promising option for achieving remission in adults with major depressive disorder – Johnson & Johnson

Johnson & Johnson announced a new analysis of Phase III data which found Caplyta (lumateperone), in combination with an antidepressant, showed significantly greater remission rates in adults with major depressive disorder (MDD) than placebo plus an antidepressant at six weeks, with continued benefits observed through six months in an open-label extension study. The findings were presented at the 64th Annual Meeting of the American College of Neuropsychopharmacology (ACNP), held in Nassau, Bahamas.

MDD is one of the most common psychiatric disorders, affecting about 22 million American adults. While remission – relief from depressive symptoms – is the ultimate goal of treatment, nearly two-thirds of patients do not achieve it with available therapies. Patients with residual symptoms experience prolonged psychosocial impairment, higher relapse risk and overall reduced quality of life. Beyond its toll on patients’ well-being, MDD has a substantial economic burden and is the leading cause of disability in the U.S.

Caplyta may help patients achieve the goal of remission
To evaluate how Caplyta may help patients achieve the goal of remission, the analysis draws from three Phase III Caplyta studies, including pooled data from two pivotal efficacy and safety trials (Studies 501 and 502) and a six-month open-label extension safety study (Study 503). The analysis evaluated three measures of remission, 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) to assess the potential resolution and durability of relief from symptoms. Across all three measures, Caplyta demonstrated meaningful remission rates, highlighting 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, M.D., Professor of Psychiatry and Chief, Division of Mood and Anxiety Disorders Treatment & Research Program, 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 six months, offering renewed hope to millions of adults seeking recovery from this disease.”

Detailed study findings
In the pooled pivotal data, almost twice as many patients reached remission (MADRS ≤10) at six weeks with adjunctive Caplyta compared to placebo (25.5 percent versus 13.6 percent; nominal p<0.0001), with 10.6 percent of patients achieving complete remission (MADRS ≤5) with Caplyta plus an antidepressant compared to 5.6 percent with placebo plus an antidepressant (p<0.01). At six weeks, significantly greater remission rates with Caplyta versus placebo were consistent across patient subgroups, including age, antidepressant type (SSRI/SNRI), and baseline severity.

In Study 503, a six-month open-label extension safety study (n = 809), efficacy was maintained with long-term Caplyta treatment, with nearly two out of three patients (65.4 percent; n = 529) reaching remission (MADRS ≤10). Complete remission (MADRS ≤5) was reached by 44.1 percent (n = 357) of patients. Notably, almost half of patients (42.8 percent; n = 346) experienced sustained remission (MADRS ≤10 at each assessment) by the end of treatment, with rates increasing steadily throughout the study: Week 8 (28.6 percent; n = 231), Week 16 (37.2 percent; n = 301), and Week 24 (40.8 percent; n = 330). 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, Ph.D., Global Therapeutic Area Head, Neuroscience, 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.”

Caplyta was recently approved by the FDA in November 2025 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. While the mechanism of action is unknown, Caplyta is characterized by high serotonin 5-HT_2A receptor occupancy and moderate amounts of dopamine D₂ receptor occupancy at therapeutic doses. Caplyta does not need dose titration, allowing patients to start treatment at the effective dose of 42 mg.

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. The medication is also being studied for other neuropsychiatric disorders. Caplyta is not FDA-approved for these disorders.

About Study 501 and Study 502
Studies 501 and 502 are two positive Phase III global, double-blind, placebo-controlled studies in patients with a primary diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who have had an inadequate response to ongoing antidepressant therapy. Caplyta, added to an antidepressant, demonstrated robust efficacy for the treatment of MDD in the primary endpoint, the MADRS Total score, with a large separation versus placebo of 4.9 points (effect size 0.61) in Study 501 and 4.5 points (effect size 0.56) versus placebo in Study 502. The efficacy of Caplyta is complemented with a favorable safety and tolerability profile – including a favorable metabolic, weight, and movement disorder profile. In the pooled safety data for Studies 501 and 502, the most commonly reported adverse events that were observed at a rate greater than or equal to 5% for lumateperone and greater than twice the rate of placebo were dizziness, dry mouth, somnolence/sedation, nausea, fatigue, and diarrhea. Importantly, metabolic and weight changes were similar to placebo and the rates of extrapyramidal symptoms were low.

About Study 503
Study 503 is a 26-week, open-label extension study that investigated the long-term safety of adjunctive Caplyta 42mg in patients who completed Study 501 or 502. The primary endpoint was safety and tolerability of Caplyta, measured by adverse events (AEs), extrapyramidal symptoms (EPS), suicidality, and changes in laboratory parameters, vital signs, and electrocardiogram (ECG) measures. The secondary endpoint was improvement/maintenance of depressive symptoms, measured by MADRS Total score and CGI-S score change from Study 501 or 502 baseline to Week 26 of open-label treatment. Mean changes from baseline to end of treatment were minimal for body morphology, cardiometabolic laboratory values, prolactin levels, pulse rate, blood pressure, and ECG measures. During the 26-week safety study, 80% of patients responded to treatment and 65% of patients experienced remission (defined as MADRS Total score ≤ 10) at 6 months. No patients reported emergence of serious suicidal ideation or suicidal behavior during the study. Symptoms of depression improved as measured by mean change from baseline to Week 26 in MADRS Total score (−22.9) and CGI-S score (−2.7).