Positive Phase III Builds Case for Intra-Cellular's Depression Drug

Pictured: Person sitting on the floor, indicating depression/Courtesy, Getty Images

Intra-Cellular Therapies’ Caplyta (lumateperone) met its primary endpoint in the Phase III Study 403 trial, easing the burden of depressive episodes in patients with major depressive disorder (MDD) or bipolar depression with mixed features.

At six weeks, patients treated with Caplyta saw an 18.2-point drop from baseline on the Montgomery Asberg Depression Rating Scale (MADRS), a diagnostic tool that measures the severity of depressive episodes. Scores in placebo comparators decreased by 12.4 points.

The between-group difference of 5.7 points was statistically significant in favor of Caplyta, according to Intra-Cellular’s announcement.

Caplyta’s advantage over placebo was also significant in the subgroup of patients with MDD or bipolar depression with mixed features.

In an investor call Tuesday morning, Suresh Durgam, M.D., executive vice president and chief medical officer, Intra-Cellular Therapies, said that in the overall study population, the statistical separation between Caplyta and placebo was apparent as early as two weeks and continued through the end of the trial. This trend was observed in both patient subgroups.

Caplyta is an oral atypical antipsychotic medication approved by the FDA in December 2019 and again in December 2021 for bipolar depression in adults. Its exact mechanism of action is still unknown. Caplyta’s effects could be due to its antagonist activity on central serotonin 5-HT2A receptors and central dopamine D2 receptors.

Intra-Cellular also ran Study 403, a randomized, double-blinded, placebo-controlled trial, to assess Caplyta in MDD. The study assessed 383 patients experiencing major depressive episodes associated with MDD or bipolar I or II disorder.

All participants also met the DSM-5 criteria for mixed features, defined as co-occurring subthreshold manic symptoms during a depressive episode or subthreshold depressive symptoms during a manic episode.

Aside from efficacy, Study 403 assessed Caplyta’s safety in MDD and found that it was generally well-tolerated, with an adverse event profile consistent with previous trials. Common side effects were nausea, dizziness and drowsiness.

Overall, 4.2% and 2.1% of the Caplyta and placebo groups dropped out due to treatment-emergent adverse events. None of the toxicities reported in the Caplyta group were deemed severe, while one such episode arose in the placebo arm.

In its approved indications, Caplyta comes with a boxed warning for higher risk of death in elderly patients with dementia-related psychosis on antipsychotic medication.

The company is preparing to approach the FDA with these data to discuss potential next steps. However, a date for the meeting has yet to be set, said Sharon Mates, Ph.D., founder, chairman and CEO, Intra-Cellular Therapies, during the investor call.