The Food and Drug Administration (FDA) has approved Caplyta (lumateperone) for the treatment of depressive episodes associated with bipolar I or II disorder in adults, as monotherapy and as adjunctive therapy with lithium or valproate. Caplyta is also indicated for the treatment of schizophrenia in adults.
The approval was supported by data from 2 global randomized, double-blind, placebo-controlled phase 3 studies (Study 404 [ClinicalTrials.gov: NCT03249376] and 402 [ClinicalTrials.gov: NCT02600507]) that evaluated the efficacy and safety of lumateperone as monotherapy and adjunctive therapy with lithium or valproate, respectively, in adults with bipolar depression. In Study 404, 381 patients were randomly assigned 1:1 to receive lumateperone 42mg orally once daily or placebo; Study 402 included 529 patients who were randomly assigned 1:1:1 to receive lumateperone 42mg, 28mg, or placebo.
The primary end point for both studies was the improvement in depression from baseline to week 6, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). A key secondary end point included the Clinical Global Impression Scale for Bipolar for Severity of Illness-Depression subscale (CGI-BP-S).
Results from Study 404 showed that lumateperone was associated with a statistically significant improvement on the MADRS total score, with a mean reduction of 16.7 points compared with 12.1 points for placebo, (least squares [LS] mean difference, -4.6 points [95% CI, -6.3, -2.8]; P <.001). Additionally, lumateperone treatment led to statistically significant improvements on the CGI-BP-S depression score.
In Study 402, lumateperone 42mg was associated with a statistically significant improvement on the MADRS total score, with a mean reduction of 16.9 points compared with 14.5 points for placebo (LS mean difference, -2.4 points [95% CI, -4.4, -0.4]; P =.0206). Lumateperone 42mg also met the key secondary end point of statistically significant improvement on the CGI-BP-S depression score.
The safety profile of lumateperone was consistent with that seen in previous studies in schizophrenia. “Caplyta has shown a consistent favorable profile on weight, cardiometabolic parameters and extrapyramidal symptoms,” noted Dr Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.
The most common adverse reactions reported with Caplyta were somnolence/sedation, dizziness, nausea, and dry mouth. A Boxed Warning related to the risk of increased mortality in elderly patients with dementia-related psychosis, as well as suicidal thoughts and behaviors in pediatric and young adult patients, has also been added to the labeling.
The product is supplied as 42mg capsules of lumateperone in 30-count boxes.
- Intra-Cellular Therapies announces US FDA approval of Caplyta® (lumateperone) for the treatment of bipolar depression in adults. News release. Intra-Cellular Therapies, Inc. Accessed December 20, 2021. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-us-fda-approval-caplytar.
- Caplyta. Package insert. Intra-Cellular Therapies, Inc.; 2021. Accessed December 20, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209500s005s006lbl.pdf.