FDA Greenlights Caplyta for Adjunctive Use in MDD

The Food and Drug Administration (FDA) has approved Caplyta^® (lumateperone) as an adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults. 

The approval was based on data from two phase 3 studies (Study 501: ClinicalTrials.gov Identifier: NCT04985942; Study 502: ClinicalTrials.gov Identifier: NCT05061706), which evaluated the safety and efficacy of lumateperone, an atypical antipsychotic, in adults who met the DSM-5 criteria for MDD, with or without anxiety. Participants enrolled were required to have an inadequate response to 1 or 2 courses of prior antidepressant therapy (ADT), defined as having less than 50% improvement after at least 6 weeks of treatment with selective serotonin or serotonin norepinephrine reuptake inhibitors or bupropion at the minimum effective dose or greater. 

Study participants (Study 501: N=485; Study 502: N=480) were randomly assigned to receive lumateperone 42mg or placebo once daily, alongside continued background ADT. The primary endpoint for both trials was change from baseline to week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.

Findings showed, compared with placebo plus ADT, adjunctive lumateperone saw a statistically significant and clinically meaningful improvement in MADRS total score in Study 501 (-14.7 points for lumateperone vs -9.8 points for placebo; difference, -4.9 [95% CI, -6.38, -3.44]) and Study 502 (-14.7 points for lumateperone vs -10.2 points for placebo; difference, -4.5 [95% CI, -6.03, -3.04]). 

Results also showed significant reductions in total Clinical Global Impression Scale-Severity scores from baseline at week 6 (key secondary endpoint) with lumateperone vs placebo in both studies (treatment difference: Study 501: -0.7 points and Study 502: -0.5 points). 

Notably, in an open-label extension safety study (ClinicalTrials.gov Identifier: NCT05061719), 80% of patients treated with lumateperone responded to treatment and 65% of patients experienced remission (MADRS total score ≤10) at 6 months. Safety findings also showed that treatment with lumateperone demonstrated a low risk of weight gain, extrapyramidal symptoms, and cardiometabolic effects.

The most common adverse reactions with treatment for MDD were dizziness, dry mouth, somnolence/sedation, nausea, fatigue, and diarrhea. Lumateperone also carries a Boxed Warning for the increased risk of mortality in elderly patients with dementia-related psychosis and for the increased risk of suicidal thoughts and behaviors. 

Caplyta is supplied as a 10.5mg, 21mg, and 42mg tablet. The recommended dose for the treatment of MDD is 42mg once daily with or without food.

In addition to the MDD indication, Caplyta is also approved for the treatment of schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder, as monotherapy or as adjunctive therapy with lithium or valproate. 

This article originally appeared on MPR