Intra-Cellular Therapies has announced top-line data from two Phase III clinical trials, study 401 and study 404, of its lumateperone as a monotherapy to treat major depressive episodes in bipolar I or bipolar II disorder patients.

Lumateperone selectively and simultaneously regulates the serotonin, dopamine, and glutamate neurotransmitter pathways, which are associated with severe mental illness.

In study 401, the investigational drug failed to meet the primary endpoint of statistical separation from placebo on the MADRS total score.

A 28mg and 42mg dose was compared to placebo in a total of 554 subjects.

The doses led to a least squares (LS) mean decrease from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 20.7 points and 18.9 points, respectively, while patients on placebo demonstrated 19.7 points.

However, the drug’s 42mg dose succeeded in meeting the primary endpoint in study 404, demonstrating statistically significant greater improvement at week six compared to placebo.

This global trial was performed in a total of 381 participants. In the intent-to-treat (ITT) population, the LS mean reduction from baseline was observed to be 16.7 points with lumateperone versus 12.1 points in the placebo group.

Lumateperone 42mg exhibited statistically significant separation from placebo at week one.

The drug candidate also met the key secondary endpoint with statistically significant improvement on the Clinical Global Impression Scale for Bipolar for Severity of Illness (CGI-BP-S) Total Score and the CGI component that specifically evaluates for depression.

Data further showed statistically significant benefits on responder as well as remission rates.

In both trials, the study drug had a favourable safety profile and was generally well-tolerated, consistent with its prior studies in schizophrenia.

Intra-Cellular Therapies chairman and CEO Dr Sharon Mates said: “The distinct pharmacological profile of lumateperone and positive clinical results in schizophrenia and bipolar depression further support the potential for benefits in a broad range of neuropsychiatric conditions, including major depressive disorder.”

The drug candidate is also being assessed in a separate Phase III trial as an adjunctive therapy to lithium or valproate for bipolar depression.