Favorable Results for Bipolar Depression Treatment

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Intra-Cellular Therapies announced the results of their phase 3 clinical trial for Caplyta (lumateperone) as a monotherapy for patients with bipolar I or bipolar II disorder experiencing a major depressive episode, published in The American Journal of Psychiatry.¹

These results demonstrate treatment with lumateperone resulted in a substantial reduction in depressive symptoms, and support the favorable safety and tolerability profile. Although lumateperone is currently indicated for the treatment of schizophrenia in adults, it has not been approved for other uses; these results show promise for treating bipolar depression.

“Bipolar depression represents the most prevalent and debilitating presentation of bipolar disorder. There is a critical need for more treatments that are effective and have favorable safety profiles,” said Gary S. Sachs, MD, Associate Clinical Professor in Psychiatry at Harvard Medical School and Founding Director of the Bipolar Clinic and Research Program at Massachusetts General. “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.”²

The global study, Study 404, randomized 381 patients with moderate to severe depression symptoms to receive either placebo or lumateperone 42 mg for 6 weeks. The primary endpoint, measured by mean change from baseline to day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score, was the efficacy of 42 mg/day of lumateperone when compared with placebo.

Treatment with lumateperone resulted in a substantial reduction in depressive symptoms. Lumateperone 42 mg was associated with a statically significant greater reduction in MADRS score from baseline to day 43 than placebo, even as early as week 1 at the first measurement. Both patients with bipolar I and bipolar II disorder saw significant improvement in MADRS Total Score in the lumateperone group compared with placebo group.

“We are excited about the robust results seen across our bipolar depression program. The 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,” said Sharon Mates, PhD, Chairman and CEO of Intra-Cellular Therapies.²

Results support the favorable safety and tolerability profile of lumateperone. The most common adverse events occurring for lumateperone 42 mg were somnolence and nausea.

The results of studies 404 and 402 form the basis of lumateperone supplemental new drug applications for the treatment of bipolar depression currently under review with FDA.

References

1. Calabrese JR, Durgam S, Satlin A, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry. 2021;appiajp202120091339.

2. Intra-Cellular Therapies. Intra-Cellular Therapies announces publication of lumateperone pivotal phase 3 study in bipolar depression in The American Journal of Psychiatry. News release. September 27, 2021. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-publication-lumateperone