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Published: Sep 27, 2021 By Mark Terry
New York-based Intra-Cellular Therapies published the results of its Study 404 phase III trial of lumateperone as monotherapy for major depressive episodes associated with bipolar I or bipolar II disorder.
The study evaluated 42 mg/day of lumateperone in patients 18 to 75 years of age with a clinical diagnosis of bipolar I or II disorder experiencing a major depressive episode. They were randomized 1:1 to receive the drug or a placebo. The primary and key secondary efficacy endpoints were changed from baseline to day 43 in score on the Montgomery-Asberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale-Bipolar Version (CGI-BP-S) severity scale, respectively.
On day 43, lumateperone demonstrated significantly greater improvement from baseline in MADRS score compared to placebo and a CGI-PB-S total score.
Along with positive data from Study 402 of lumateperone as adjunctive therapy with lithium or valproate, this data supported the drug as a new treatment for this indication. Studies 404 and 402 are the basis of Caplyta (lumateperone)’s supplemental New Drug Application (sNDA) for bipolar depression that is currently being reviewed by the U.S. Food and Drug Administration (FDA). Intra-Cellular has a target action date of December 17, 2021.
“Bipolar depression represents the most prevalent and debilitating presentation of bipolar disorder,” said Gary S. Sachs, Associate Clinical Professor in Psychiatry at Harvard Medical School and Founding Director of the Bipolar Clinic and Research Program at Massachusetts General. “There is a critical need for more treatments that are effective and have favorable safety profile. The strong efficacy and impressive safety results reported in this trial for a broad patient population position lumateperone as a potentially important advancement in the treatment of this disorder.”
Caplyta is already approved for schizophrenia in adults. The mechanism of action of the drug in schizophrenia is unknown. The efficacy may be mediated via a combination of antagonist activity at central serotonin 5-H2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.
“We are excited about the robust results seen across our bipolar depression program,” stated Sharon Mates, Chairman and Chief Executive Officer of Intra-Cellular Therapies. “This study reported on today, Study 404, our monotherapy study, along with Study 402, our adjunctive study with lithium or valproate form the basis of our supplemental NDAs under FDA review. If approved, we plan to launch immediately and look forward to bringing Caplyta to market for the treatment of bipolar depression.”
On September 20, the company published four manuscripts on its lenrispodun and possible cardiovascular therapeutic effects of Phosphodiesterase Type 1 (PDE1) inhibition.
“PDE1 inhibition restores intracellular signaling by elevating the second messengers cAMP and cGMP in certain pathological states associated with low levels of these signaling molecules,” said Robert Davis, Senior Vice President and Chief Scientific Officer, Intra-Cellular. “PDE1 enzymes require calcium and calmodulin for their activation and are expressed in multiple tissues including smooth and cardiac muscle, neurons, and macrophages/microglia providing opportunities to treat multiple diseases.”
The company’s PDE1 inhibitor portfolio is targeting diseases where the PDE1 enzyme is over-expressed and/or abnormal immune cell function adds to disease pathology. This includes Parkinson’s disease, heart failure, and some cancers.
Lenrispodun is a potent and selective PDE1 inhibitor, the lead compound of the company’s PDE1 portfolio. It is under development for Parkinson’s and heart failure.
The Lumateperone Pivotal Phase III Study in bipolar depression is published online in The American Journal of Psychiatry.
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