Intra-Cellular Therapies announced positive topline results from its Phase 3 clinical trial (Study 402) evaluating lumateperone as adjunctive therapy to lithium or valproate in the treatment of major depressive episodes associated with Bipolar I or Bipolar II disorder. In Study 402, once daily lumateperone 42 mg met the primary endpoint for improvement in depression as measured by change from baseline versus placebo on the MADRS total score (p=0.0206; effect size = 0.27). Lumateperone 42 mg also met the key secondary endpoint, the CGI-BP-S Depression Score (p=0.0082; effect size = 0.31). The lower lumateperone dose, 28 mg, showed a trend for a dose-related improvement in symptoms of depression but the results did not reach statistical significance. Lumateperone demonstrated a favorable safety profile and was generally well-tolerated in the trial. The most commonly reported adverse events that were observed at a rate greater than or equal to 5% and at least twice the rate of placebo were somnolence, dizziness, and nausea. Rates of akathisia, restlessness, extrapyramidal symptoms, and changes in weight were similar to placebo. This trial, in conjunction with our previously reported positive Phase 3 monotherapy study, Study 404, forms the basis for our sNDA for the treatment of bipolar depression in patients with Bipolar I or II disorder as monotherapy and adjunctive therapy which we expect to submit to the FDA in late 2020 or early 2021.

“Our program now has confirmatory evidence of efficacy and a favorable safety and tolerability profile of lumateperone in bipolar depression; we look forward to submitting our supplemental NDA to expand lumateperone’s label to include a second major neuropsychiatric disorder,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “With this clinical milestone, lumateperone has shown further potential to benefit patients suffering from a range of serious mental health conditions in addition to schizophrenia.”

“Bipolar disorders are serious and complex mental health conditions that affect millions of people, and depression is the most common presentation of these disorders. In this study, lumateperone demonstrated a robust effect, which is particularly significant considering patients were maintained on lithium or valproate,” said Dr. Roger McIntyre, Professor of Psychiatry and Pharmacology at the University of Toronto and Head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto, Canada. “Lumateperone is the first treatment to demonstrate efficacy for bipolar depression as monotherapy and as adjunctive therapy to mood stabilizers in a study population including both Bipolar I and Bipolar II patients. This will be welcome news to the psychiatric community as there is a tremendous need for improved treatment options.”

Study 402 was conducted globally in five countries including in the U.S. A total of 529 patients with moderate to severe major depressive episodes associated with either Bipolar I or Bipolar II disorder were randomized 1:1:1 to lumateperone 42 mg, 28 mg or placebo, while being maintained on lithium or valproate as mood stabilizers.

Lumateperone 42 mg met the primary endpoint by demonstrating a statistically significant improvement compared to placebo at week 6 (trial endpoint), as measured by change from baseline on the MADRS total score. In the intent-to-treat (ITT) study population, the least squares (LS) mean reduction from baseline for lumateperone 42 mg was 16.9 points, versus 14.5 points for placebo (LS mean difference = 2.4 points; effect size = 0.27, p=0.0206).

Lumateperone 42 mg also met the key secondary endpoint of statistically significant improvement on the CGI-BP-S Depression Score (p=0.0082; effect size = 0.31).

Lumateperone 28 mg showed a trend for a dose-related improvement in symptoms of depression. Though not formally tested against placebo since it did not separate on the primary endpoint, lumateperone 28 mg demonstrated a statistically significant improvement versus placebo on the CGI-BP-S.

Lumateperone was generally well-tolerated with a favorable safety profile in the trial. Adverse events were mostly mild to moderate and similar to those seen in prior studies in bipolar depression and schizophrenia, with no new adverse events observed. These findings provide further evidence supporting lumateperone’s favorable safety and tolerability profile across different patient populations.