공시 • May 05
Johnson & Johnson Shows Greatest Improvement Across Key Efficacy Outcomes for Caplyta (Lumateperone) Among Adjunctive Mdd Treatments in New Network Meta-Analysis
Johnson & Johnson announced findings from the first network meta-analysis (NMA) comparing CAPLYTA® (lumateperone) to FDA-approved atypical antipsychotics for add-on treatment of major depressive disorder (aMDD) in adults, drawing on data from 10 registrational randomized clinical trials. The NMA found that CAPLYTA® was favored for the efficacy outcomes across four measures, based on indirect comparisons derived from placebo plus antidepressant therapy (ADT)-controlled trials. The analysis also evaluated safety outcomes, with CAPLYTA® demonstrating no statistically significant weight gain compared to placebo plus ADT and favorable rankings on select tolerability measures. The data were featured in a late-breaking presentation at the 2026 Neuroscience Education Institute (NEI) Spring Congress, held from May 1-3, in Kissimmee, Florida. The NMA is a widely used method to indirectly compare treatments evaluated in separate placebo-controlled trials. To reflect clinical decision-making at the treatment level, doses were pooled within treatments in this analysis, resulting in a star-shaped network comprising five treatment nodes anchored on placebo plus ADT. Outcomes were selected based on availability of data across the identified clinical trials and comprised four efficacy outcomes – change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score, MADRS response, MADRS remission, and change from baseline in CGI-S score – and four safety outcomes: weight change from baseline, incidence of clinically meaningful weight increase, akathisia, and somnolence. Additional safety and tolerability outcomes were not assessed in this NMA due to inconsistent reporting across trials. Efficacy: CAPLYTA® was favored for the efficacy outcomes across four measures, with the largest effect size among all five treatment nodes evaluated: MADRS change from baseline (mean difference [MD] -4.71; 95% credible intervals [CrI] -5.78, -3.63), MADRS response (odds ratio [OR 2.33]; 95% CrI 1.77, 3.05), MADRS remission (OR 2.22; 95% CrI 1.57, 3.07), and CGI-S change from baseline (MD -0.60; 95% CrI -0.74, -0.46). In pairwise treatment comparisons anchored to CAPLYTA®, CAPLYTA® was favored across all comparators for MADRS and CGI-S change from baseline, and versus all but one comparator for MADRS response and MADRS remission. Weight: CAPLYTA® demonstrated no statistically significant weight gain compared to placebo plus ADT, ranking most favorably among all treatments evaluated on both weight-related outcomes: mean weight change from baseline (MD -0.08; 95% CrI -0.30, 0.13; 77% probability of superiority) and proportion of patients with a clinically meaningful weight increase of =7% (OR 0.41; 95% CrI 0.04, 1.42; 94% probability of lower risk). CAPLYTA® had a 100% probability of superiority versus all comparators on mean weight change. Akathisia (inner restlessness): CAPLYTA® was the only treatment comparable to placebo plus ADT for the risk of akathisia (OR 3.78; 95% CrI 0.40, 17.17); the remaining four treatments evaluated showed higher akathisia risk than placebo plus ADT. Somnolence: Somnolence risk was higher than placebo plus ADT across all treatments evaluated (CAPLYTA® OR 5.90; 95% CrI 2.86, 11.50). In pairwise comparisons, CAPLYTA® showed comparable risk versus two treatments and higher risk versus two treatments. NMA is a structured, protocol-driven analytical process widely accepted and utilized by regulatory agencies, health technology assessment agencies, and medical guideline committees to compare treatment options when head-to-head trials are limited or unavailable. As NMAs rely on indirect comparisons across studies that can differ in design and patient populations, findings should be interpreted cautiously alongside the totality of evidence, including individual trial results and clinical considerations. The NMA evaluated the comparative efficacy and safety of five atypical antipsychotics approved by the FDA as adjunctive therapy for adults with MDD, including aripiprazole (Abilify®), brexpiprazole (Rexulti®), cariprazine (Vraylar®), lumateperone (CAPLYTA®) and quetiapine XR (Seroquel XR®). The analysis included 10 randomized, double-blind, parallel-group, placebo-controlled trials identified through a systematic literature review using Section 14: Clinical Studies in the U.S. Prescribing Information of each of the five products. A Bayesian statistical framework with a star-shaped network design was used, with ADT plus placebo as the common comparator, enabling indirect comparative estimates for efficacy outcomes (MADRS change from baseline, MADRS response, MADRS remission, and CGI-S change from baseline) and safety outcomes (weight change from baseline, weight increase of 7% or more, akathisia, and somnolence). This NMA adheres to all governing standards and requirements as demanded by global health technology assessment agencies, journal review committees and regulatory authorities. The NMA was funded by Janssen Research & Development, LLC. CAPLYTA® 42 mg is an oral, once daily atypical antipsychotic approved in adults as an adjunctive therapy with antidepressants for major depressive disorder (MDD), schizophrenia, and depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy, and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA® is unknown, the efficacy of CAPLYTA® could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and partial agonist activity at central dopamine D2 receptors. A supplemental New Drug Application (sNDA) for CAPLYTA® with long-term data evaluating the safety and efficacy of the medication for delayed time to relapse in schizophrenia was recently approved by the U.S. Food and Drug Administration. The medication is also being studied for other neuropsychiatric disorders. CAPLYTA® is not FDA-approved for these disorders. CAPLYTA® (lumateperone) is a prescription medicine used in adults along with an antidepressant to treat major depressive disorder (MDD); to treat depressive episodes associated with bipolar I or bipolar II disorder (bipolar depression) alone or with lithium or valproate; or to treat schizophrenia. It is not known if CAPLYTA is safe and effective in children. Medicines like CAPLYTA can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). CAPLYTA is not approved for treating people with dementia-related psychosis.
