Intra-Cellular Therapies, Inc. (NASDAQ: ITCI) has submitted a supplemental new drug application (SNDA) to the U.S. Food and Drug Administration (FDA) for Caplyta (lumateperone) for the treatment of major depressive disorder (MDD) in adults as adjunctive therapy to antidepressants. This submission is based on positive results from studies 501 and 502, demonstrating Caplyta's robust antidepressant efficacy and favorable safety and tolerability profile. Caplyta, if approved as an adjunctive therapy in MDD, would be indicated for the treatment of three different major psychiatry indications affecting over 30 million adult patients in the US.
The studies 501 and 502, which form the basis of the SNDA, are two positive phase 3 global, double-blind, placebo-controlled studies in patients with a primary diagnosis of MDD according to the DSM-5 criteria who have had an inadequate response to ongoing antidepressant therapy. Caplyta, added to an antidepressant, demonstrated robust efficacy for the treatment of MDD in the primary endpoint, the Montgomery Asberg Depression Rating Scale (MADRS) total score, with a large separation versus placebo of 4.9 points (effect size 0.61) in study 501 and 4.5 points (effect size 0.56) versus placebo in study 502.
Caplyta's efficacy is complemented with a favorable safety and tolerability profile, including a favorable metabolic, weight, and movement disorder profile. In the pooled safety data for studies 501 and 502, 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. Importantly, metabolic and weight changes were similar to placebo, and the rates of extrapyramidal symptoms were low.
Major depressive disorder (MDD) is a common mood disorder in the U.S., affecting an estimated 21 million adults each year. Depressive disorders are the second cause of years lived with disability in the world. Symptoms include sadness, hopelessness, helplessness, feelings of guilt, irritability, loss of interest in formerly pleasurable activities, cognitive impairment, disturbed sleep patterns, and suicide ideation or behavior. MDD can cause severe functional impairment, adversely affecting interpersonal relationships, and may impact quality of life. Approximately two-thirds of patients with depression fail to achieve remission with first-line treatment.
Caplyta (lumateperone) is already indicated in adults for the treatment of schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.
The most common adverse reactions in clinical trials with Caplyta versus placebo were somnolence/sedation, dizziness, nausea, and dry mouth. Caplyta is available in 10.5 mg, 21 mg, and 42 mg capsules.
Caplyta 42 mg is an oral, once-daily atypical antipsychotic approved in adults for the treatment of schizophrenia and the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of Caplyta is unknown, the efficacy of Caplyta could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.
Intra-Cellular Therapies is a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, leveraging an intracellular approach to developing innovative treatments for people living with complex psychiatric and neurologic diseases. As a result of these announcements, the company's shares have moved -1.1% on the market, and are now trading at a price of $85.1. Check out the company's full 8-K submission here.
