Lundbeck and Otsuka's Antipsychotic Drug Rexulti Fails Two Bipolar Phase III Trials

Denmark’s H. Lundbeck A/S and Japan’s Otsuka Pharmaceutical announced that their brexpiprazole failed to meet its primary endpoint in two Phase III clinical trials to treat manic episodes in patients with bipolar I disorder. The drug was approved by the U.S. Food and Drug Administration (FDA) in July 2015 for adjunctive therapy to antidepressants in adults with major depressive disorder and for adults with schizophrenia. It was also approved in Europe and Canada in 2018 and 2017, respectively, to treat schizophrenia. It is marketed under the brand name Rexulti in non-European markets and as Rxulti in Europe.
The drug was tested in two multicenter clinical trials compared to placebo in about 650 bipolar I patients who had acute manic episodes, with or without mixed features, that were severe enough to require hospitalization. The primary endpoint was statistical separation as measured by the Young Mania Rating Scale (YMRS) at three weeks. The companies indicated that the placebo effect on the rating scales was much higher than expected. The drug was typically well tolerated. They expect to continue analysis to decide what to do next. The data from these trials don’t have any effect on the already approved indications for major depressive disorder and schizophrenia.