Caplyta reduces bipolar disorder-associated depressive episodes

Caplyta reduced depression symptoms in patients with major depressive episodes linked to bipolar I and bipolar II disorders, according to a phase 3 randomized placebo-controlled trial in American Journal of Psychiatry.

“Depressive episodes tend to last longer, are more difficult to treat and recur more often than manic or hypomanic episodes,” Suresh Durgam, MD, chief medical officer of Intra-Cellular Therapies Inc., told Healio Psychiatry. “Given there are only a few drugs FDA approved to treat bipolar I depression, and only one treatment currently approved for bipolar II depression, we wanted to evaluate lumateperone in this area with the ultimate goal of providing a new treatment option for patients.”

Durgam and colleagues examined the efficacy and safety of 42 mg per day of Caplyta (lumateperone, Intra-Cellular Therapies) among patients with bipolar I or bipolar II disorder who experienced a major depressive episode. They randomly assigned in a 1:1 ratio 188 patients to 42 mg per day of lumateperone and 189 to placebo, with oral administration once daily in the evening for 6 weeks. Change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale–Bipolar Version severity scale (CGI-BP-S) served as the primary and key secondary endpoints, respectively. The researchers included treatment-emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms and suicidality in safety assessments.

Results showed an association between lumateperone treatment and significantly greater improvement from baseline in MADRS score vs. placebo and CGI-BP-S total score, for effect sizes of −0.56 and −0.46, respectively. Durgam and colleagues noted significant MADRS superiority for lumateperone vs. placebo among patients with bipolar I and bipolar II disorders. They reported somnolence and nausea as the only treatment-emergent adverse events that occurred with lumateperone at a clinically meaningful greater rate compared with placebo.

Further, the researchers observed a low incidence of extrapyramidal symptom-related treatment-emergent adverse events that was similar to that for placebo. Changes in weight, vital signs or metabolic or endocrine assessments were minimal.

“The results from this study, in conjunction with the positive results of a second phase 3 study evaluating lumateperone as an adjunctive treatment with lithium or valproate, form the basis of Caplyta’s supplemental new drug applications for the treatment of bipolar depression as monotherapy and as adjunctive therapy with lithium or valproate currently under review with the FDA, with PDUFA action date of Dec. 17 of this year,” Durgam said.