Minerva Neurosciences Announces Positive Top Line Results in Phase 2b Clinical Trial With Seltorexant (MIN-202) in Treatment of Depressed Patients With an Inadequate Response to SSRIs and SNRIs
- Potential first-in-class, oral specific orexin-2 inhibitor demonstrates statistically significant improvement in MADRS scores at 6 weeks compared to placebo
- Well tolerated, with adverse events similar to or lower than the rate observed in the placebo group
- Improves depressive symptoms and sleep function, thus differentiating seltorexant from current therapies
- Demonstrates improvement in symptoms of MDD patients not adequately treated by SSRIs and/or SNRIs, a significant unmet need
- Data support ongoing development of seltorexant in MDD
In this dose finding study, the 20 milligram (mg) dose of seltorexant, under co-development with
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.
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.”
About the Phase 2b study (aMDD2001)
The multicenter, double-blind, randomized, parallel-group, placebo-controlled, 6-week adaptive dose-finding study consisted of three phases: a screening phase lasting up to 4 weeks, a 6-week double-blind treatment phase and a 2-week post-treatment follow-up phase. In total, 287 adult patients were enrolled at 84 clinical sites in the U.S.,
At commencement of study enrollment, subjects were randomly assigned to receive 1 of 3 treatments in a 2:1:1 ratio of seltorexant to placebo (20 mg, 40 mg). After a pre-planned interim analysis (IA), subjects were randomly assigned to receive 1 of 3 treatments in a 3:3:1 ratio of seltorexant to placebo (10 mg, 20 mg). The randomization was stratified by region (U.S.,
Seltorexant and the Major Depressive Disorder (MDD) landscape
Major Depressive Disorder (MDD) is one of the most commonly encountered mental disorders, with a prevalence rate in
Among those patients suffering from MDD disorders, some do not respond adequately to either SSRIs or SNRIs. Inadequate response to these pharmacological treatments is a major challenge to worldwide public health. Although it is widely considered that current intervention benefits approximately 60% of MDD patients, only about 30% to 40% of patients show full remission of their symptoms as defined by the MacArthur criteria (for example, a 17-item Hamilton Depression Rating Scale (HDRS) score < 8).
To overcome the lack of adequate response, the use of atypical antipsychotics as adjunctive therapy for the management of patients with an inadequate response to standard of care has become one of the most widely used therapeutic strategies. Use of adjunctive atypical antipsychotics for MDD is associated with significant side effects such as weight gain, akathisia, and sedation. Several other approaches have been evaluated but, in most cases, with non-conclusive results.
Innovative approaches are needed to improve current response rates to existing treatments. The orexin system is viewed as a pivotal system in the brain and its effects classically include promotion of feeding, maintaining homeostasis, arousal, modulation of sleep-wake circadian cycles and motivation. These functions are mediated via two orexin receptors, ORX1 and ORX2.
Seltorexant is the most advanced specific ORX2 molecule in clinical development with antagonistic activity when binding to its receptor. Seltorexant is currently being developed in two indications, specifically insomnia without associated psychiatric disorders and MDD in patients who have an inadequate response to SSRIs and SNRIs. Previous clinical trials have indicated that seltorexant might be useful in both indications.
About Seltorexant (MIN-202)
Seltorexant is a selective orexin-2 receptor antagonist under co-development by
About the Minerva & Janssen collaboration
Minerva is developing seltorexant with Janssen Pharmaceutica, a
Minerva has no financial obligations for development costs until completion of the Phase 2b development milestone. Minerva has strategic control of matters relating to the clinical development of seltorexant for insomnia.
Forward-Looking Safe Harbor Statement
This press release contains forward-looking statements which are subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of this press release, and involve certain risks and uncertainties. Forward-looking statements include statements herein with respect to the timing and scope of current clinical trials and results of clinical trials with roluperidone, seltorexant, MIN-117 and MIN-301; the timing and scope of future clinical trials and results of clinical trials with these compounds; the clinical and therapeutic potential of these compounds; our ability to successfully develop and commercialize our therapeutic products; the sufficiency of our current cash position to fund our operations; and management’s ability to successfully achieve its goals. These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors including, without limitation, whether roluperidone, seltorexant, MIN-117 and MIN-301 will advance further in the clinical trials process and whether and when, if at all, they will receive final approval from the
VP, Investor Relations/
Source: Minerva Neurosciences, Inc