Intra-Cellular Therapies, Inc has submitted supplemental New Drug Applications (sNDAs) to the Food and Drug Administration (FDA) for the use of lumateperone in the treatment of depressive episodes associated with bipolar I or II disorder, both as monotherapy and as adjunctive therapy.
The sNDA submissions are 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; effect size = 0.56; P <.001) in the intent-to-treat (ITT) study population. Additionally, lumateperone treatment led to statistically significant improvements on the CGI-BP-S total score (effect size = 0.46; P <.001) and on the CGI component that assesses depression (CGI-BP-S Depression Score; effect size =0.50; P <.001).
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; effect size =0.27; P =.0206) in the ITT population. Lumateperone 42mg also met the key secondary end point of statistically significant improvement on the CGI-BP-S Depression score (effect size =0.31; P =.0082).
The safety profile of lumateperone in both studies was consistent with that seen in previous studies in schizophrenia. The most common adverse events reported (incidence of greater than or equal to 5% and at least twice the rate of placebo) were somnolence, dizziness and nausea. The rates of akathisia, restlessness and extrapyramidal symptoms for lumateperone were low and similar to placebo.
Lumateperone, an atypical antipsychotic, is marketed under the brand name Caplyta® and is currently approved for the treatment of schizophrenia in adults.
- Intra-Cellular Therapies applies for FDA approval of Caplyta® (lumateperone) for the treatment of bipolar depression. [press release]. New York, NY: Intra-Cellular Therapies, Inc; February 22, 2021.
- Intra-Cellular Therapies announces positive topline results from study 402 evaluating lumateperone as adjunctive therapy in patients with bipolar depression. [press release]. New York, NY: Intra-Cellular Therapies, Inc; September 9, 2020.
- Intra-Cellular Therapies announces positive top-line results from a phase 3 trial of lumateperone in patients with bipolar depression. [press release]. New York, NY: Intra-Cellular Therapies, Inc; July 8, 2019.