Sunovion Announces Topline Results from Global Phase 2 Study of SEP-4199 in Patients with Bipolar I Depression
Sunovion Pharmaceuticals Inc. (Sunovion) announced topline results from study SEP380-201, a global, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety, and tolerability of treatment with SEP-4199, an investigational oral medicine for the treatment of major depressive episodes associated with bipolar I disorder (bipolar I depression). SEP-4199 is a non-racemic ratio of amisulpride enantiomers with increased potency for serotonin 5-HT7 receptors relative to dopamine D2 receptors.
According to the topline results for the primary endpoint, which included data from Europe and the U.S., in patients with bipolar I depression, SEP-4199 showed numerical improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo after six weeks of treatment (200 mg: -19.5 vs -16.2, 400 mg: -19.3 vs -16.2 respectively, both dose groups vs placebo, p=0.054; 200 mg group effect size (ES) = -0.31 and 400 mg group ES = -0.29). While the study did not meet its primary endpoint, a relatively large improvement in MADRS total score was observed in the placebo group, which may have contributed to the trend level findings of the primary analysis.
In a pre-specified exploratory analysis of data from all 337 Intent-To-Treat patients, including those enrolled in Japan, the least squares (LS) mean reduction from baseline at Week 6 in MADRS total score was -18.0 and -17.7 for the SEP-4199 200 mg and 400 mg doses, respectively, and -14.3 for placebo, resulting in LS mean differences from placebo of -3.7 and -3.4, for the 200 mg and 400 mg doses, respectively, (unadjusted p-values <0.025, ES of -0.34 and -0.31, respectively). These results suggest that patients with bipolar I depression treated with SEP-4199 in both dose groups experienced clinically meaningful improvements over the study period.
SEP-4199 was well-tolerated by patients enrolled in the study, with relatively low rates of adverse events. The most commonly reported adverse events occurring more frequently in the SEP-4199 treatment group than in the placebo group, and in at least two percent of patients, included QT prolongation (observed in the 400 mg arm), somnolence, constipation, galactorrhea, nausea, akathisia, dizziness, hypomania and diarrhea. Serious adverse events were reported by two patients in the study, including one patient treated with SEP-4199 and one patient who received placebo.
“Major depressive episodes associated with bipolar disorder can be difficult to treat and there is a pressing need for additional treatment options,” said Maurizio Fava, MD, Chief of the Department of Psychiatry at Massachusetts General Hospital. “I am encouraged by these topline findings. Despite the high placebo response in this study, which is known to diminish the effect size and the ability to detect a signal, the topline results suggest that SEP-4199 has the potential to be an effective advance in treatment for people with bipolar depression.”
“SEP-4199 is a prime example of how Sunovion’s deep expertise and understanding of unmet medical needs leads our scientists to create novel solutions for people with serious neuropsychiatric conditions like bipolar depression,” said Kenneth Koblan, PhD, Chief Scientific Officer of Sunovion. “The topline efficacy results of this study, coupled with the tolerability profile, provides us with confidence in the potential of SEP-4199 as a novel treatment option for people living with bipolar depression. The results of this study will guide us as we consider our plans to start Phase 3 studies. We look forward to presenting the full study data and discussing them with the scientific community at future medical meetings.”