Lumateperone, an investigational drug from Intra-Cellular Therapies, Inc., posted varied results in two phase 3 clinical trials evaluating it as a monotherapy for major depressive episodes associated with bipolar disorder.
Study 404 was conducted globally, including in the United States, and randomized 381 patients to lumateperone 42 mg or placebo. The drug met the primary endpoint for improvement in depression, as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), and its key secondary endpoint, the Clinical Global Impression Scale for Bipolar for Severity of Illness Total Score.
The study also showed statistically significant improvements in responder and remission rates and within patients subgroups.
“It is rather difficult to obtain positive studies with bipolar depression so every time, no matter what the medication is, a positive study in bipolar depression is cause for celebration,” Psych Congress cochair Rakesh Jain, MD, MPH, said. “The unmet needs with bipolar depression are so extensive.”
In Study 401, conducted solely in the United States, 554 patients were randomized to lumateperone 42 mg or 28 mg or placebo. Neither dose met the primary endpoint of statistical separation from placebo in the MADRS total score. There was a high placebo response in the trial, Intra-Cellular reported.
“Studies in bipolar disorder often encounter negative results and that often has to do with high placebo response rates,” said Dr. Jain, also Clinical Professor, Department of Psychiatry, Texas Tech Health Sciences Center School of Medicine – Permian Basin, Midland, Texas. “Over the course of the last decade or two, placebo response rates have been magnified for reasons not fully understood..”
About 50% of studies involving bipolar depression produce negative results, Dr. Jain pointed out. “One study does not itself inform us about all the positive and negative issues with a medication,” he said. “One must take the totality of the data in order to fully appreciate the efficacy and side effect profile of any medication.”
In both studies, lumateperone was well-tolerated, with a favorable safety profile and low discontinuation rates due to treatment-emergent adverse events for both doses, according to a statement from Intra-Cellular. The rates of akathisia, restlessness, and extrapyramidal symptoms combined were less than 1% and similar to placebo in both trials.
Dr. Jain said akathisia can be a significant challenge for patients with bipolar depression, and sometimes leads to treatment discontinuation.
“I was pleased to see that the side effect burden created by lumateperone was quite favorable in terms of the risk of akathisia,” Dr. Jain said. “I very much look forward to the ultimate approval of this medication by the FDA in due course and to having it available as a treatment option for me to help my patients.”
Lumateperone is being evaluated by the US Food and Drug Administration as a treatment for schizophrenia.
Intra-Cellular Therapies announces positive top-line results from a phase 3 trial of lumateperone in patients with bipolar depression [press release]. New York, NY: Intra-Cellular Therapies; July 8, 2019.
Editor's note: This story has been updated from a previous version.