FDA Review Sought for Lumateperone as Adjunctive Therapy for Major Depressive Disorder

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Intra-Cellular Therapies announced they submitted a supplemental New Drug Application (sNDA) to the US FDA for lumateperone (Caplyta) for the treatment of major depressive disorder (MDD) in adults as adjunctive therapy to antidepressants.

“MDD is a highly prevalent condition with a significant need for efficacious, safe, and well-tolerated medicines, as more than half of patients do not adequately respond to an antidepressant alone,” Suresh Durgam, MD, executive vice president and chief medical officer of Intra-Cellular Therapies, said in a press release.

The sNDA submission was based on positive findings from two phase 3 global, double-blind, placebo-controlled trials in people with a primary diagnosis of MDD, as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, who have had an inadequate response to antidepressants. Data from studies 501 and 502 showed that lumateperone, when added to antidepressant treatment, demonstrated robust efficacy for MDD in the primary endpoint, the Montgomery Asberg Depression Rating Scale (MADRS) total score, with a large separation compared to placebo of 4.9 points (effect size 0.61) in study 501 and 4.5 points (effect size 0.56) vs placebo in study 502.

In addition, lumateperone also demonstrated a favorable safety and tolerability profile, including a favorable metabolic, weight, and movement disorder profile. In the pooled safety data for both trials, the most commonly reported adverse events that were observed at a rate greater than or equal to 5% for lumateperone and greater than twice the rate of placebo were dizziness, dry mouth, somnolence/sedation, nausea, and fatigue. Metabolic and weight changes were similar to placebo and the rates of extrapyramidal symptoms were low, according to the press release.

“Given CAPLYTA’s efficacy and safety profile, we believe CAPLYTA can become a first-choice treatment for the adjunctive treatment of MDD pending FDA approval, and we look forward to working with the FDA during this review process,” Durgam said.

Lumateperone (10.5 mg, 21 mg, and 42 mg) is an oral, once daily atypical antipsychotic already approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder as monotherapy and as adjunctive therapy with lithium or valproate. Lumateperone does not have a known mechanism of action, but Intra-Cellular Therapies wrote in the release that lumateperone could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Reference: Intra-Cellular Therapies submits supplemental New Drug Application (sNDA) to FDA for CAPLYTA® (lumateperone) for the treatment of major depressive disorder as adjunctive therapy. News release. Intra-Cellular Therapies. December 3, 2024. Accessed December 13, 2024. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-submits-supplemental-new-drug