Minerva Neurosciences, Inc., a clinical-stage biopharmaceutical company focused on the development of therapies to treat central nervous system (CNS) disorders, announced positive results from a Phase 2b clinical trial of seltorexant (MIN-202) as adjunctive therapy to antidepressants in adult patients with major depressive disorder (MDD) who have responded inadequately to selective serotonin reuptake inhibitors (SSRIs) and/or serotonin-norepinephrine reuptake inhibitors (SNRIs).
In this dose finding study, the 20 milligram (mg) dose of seltorexant, under co-development with Janssen Pharmaceutica NV, showed a statistically significant improvement in the MADRS (Montgomery-Asberg Depression Rating Scale) score compared to placebo. The least squares mean (LS mean) difference from placebo of the change in MADRS total score at the end of week 6 was 3.1 for the 20 mg dose of seltorexant, and the 2-sided p-value was 0.083, which is below the pre-specified 2-sided type I error level of 0.1.
After three weeks of treatment, seltorexant at the 20 mg dose also showed a statistically significant improvement over placebo, highlighting its ability to improve mood symptoms over a short period of time. In addition, a key secondary outcome measure, which was based on patient stratification according to baseline insomnia severity index (ISI), showed an even greater difference from placebo for the seltorexant 20 mg arm in patients with clinically significant insomnia (ISI ≥ 15) with LS mean difference versus placebo of 4.9 on the MADRS total score and a 2-sided p-value of 0.050 compared to the overall patient population in this trial.
The 40 mg dose, to which further enrollment was stopped following the interim analysis, showed an improvement in the MADRS total score versus placebo at the end of week 6 but did not reach statistical significance. Results for the 10 mg dose were not interpretable due to the small sample size of patients assigned to this dose.
Seltorexant was well tolerated, and adverse events recorded were similar to those observed in previous studies and similar to or lower than the rate observed in the placebo group.
“Results of this study represent the first clinical observation in a large, late-stage study that a selective orexin molecule can achieve a positive effect as an adjunctive treatment in patients with MDD who have an inadequate response to SSRIs and SNRIs,” said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer of Minerva. “These findings, if confirmed in Phase 3 studies, point to a completely novel approach which would give hope to patients and to the professionals who treat them for a potential new treatment for MDD with an improved safety profile compared to existing therapies. Around 60%-70% of patients diagnosed and treated with first-line therapies, including SSRIs and/or SNRIs, do not experience adequate treatment response, and seltorexant potentially represents a unique opportunity to improve treatment response rates safely in most of these patients.”
Dr. Luthringer added, “The top line results from a separate Phase 2b trial of seltorexant in insomnia, now completely enrolled, are expected to be announced later this quarter and will add to the body of clinical data with seltorexant in insomnia and MDD.”