Intra-Cellular Therapies has announced positive topline results from a Phase III study of Caplyta (lumateperone) as a monotherapy for patients with major depressive disorder (MDD) with mixed features and bipolar depression with mixed features.
The 488-patient Phase III trial (NCT04285515), also known as Study 403, met its primary endpoint of symptom reduction along the Montgomery-Asberg Depression Rating Scale (MADRS). MADRS is a ten-item, psychiatrist assessment of depressive episodes in patients with mood disorders. Intra-Cellular’s Phase III trial also met its key secondary endpoint of clinician’s assessment of improvement in the overall severity on the Global Impression of Severity Scale (CGI-S).
Mixed features in MDD and bipolar depression describe patients who experience manic symptoms during depressive episodes or depressive symptoms during manic episodes.
In the overall Phase III trial population, Caplyta reduced MADRS by 5.7 points versus placebo (p<0.0001). This includes a 5.9-point reduction in MDD with mixed features and a 5.7-point reduction in bipolar depression with mixed features. As for safety, the most commonly reported adverse events were somnolence, dizziness, and nausea.
Caplyta has FDA approval for the treatment of schizophrenia and depressive episodes associated with bipolar disorder as monotherapy and as adjunctive therapy with lithium or valproate. Though Caplyta’s exact mechanism is unknown, it is thought that the drug could act on central serotonin 5-HT2A receptors and central dopamine D2 receptors.
Unmet needs in major depressive disorder and bipolar depression
MDD effects approximately 21 million people in the US each year, and recent studies have suggested MDD can worsen other conditions ranging from multiple sclerosis to atopic dermatitis. Despite an uptick in recent MDD trial activity centered in the US and China, the field as a whole still faces key challenges designing studies and developing effective biomarkers. New research has also indicated that the Covid-19 pandemic exasperated the incidence of depression and other mental health conditions.
Meanwhile, bipolar disorders affect approximately 11 million people in the US, with bipolar depression presenting as the most common form of the psychiatric condition. In the bipolar disorder pipeline, analysts expect lithium to maintain its place as the gold standard for treatment.
That said, there is room for drugs like Caplyta to work in patients alongside lithium standard of care. Analysts also note there are opportunities for drugs like Caplyta to demonstrate long-term efficacy in bipolar disorder and fill a key unmet patient need.