It does not take much digging to find reasons for Minerva Neurosciences’ 14% share price drop today, in the wake of a press release heralding “positive” results for its depression project, seltorexant. The lack of dose response immediately raises a red flag, as does the mention of only one secondary endpoint – 19 are specified in the trial design. Throw in a controversial use of statistics, and it is no wonder that investors are unconvinced. The study, in 287 patients with major depressive disorder, tested three doses of seltorexant. A 40mg dose cohort was stopped at an interim analysis, while a 10mg cohort was “not interpretable” due to the small sample size. Bang in the middle is the sweet spot, according to Minerva: the 20mg group showed a statistically significant improvement on the MADRS depression scale compared with placebo, with a p value of 0.083. This would normally be considered a fail, of course, but Minerva employed a two-sided p-value test, with a pre-specified type 1 error level of 0.1. Shareholders will be hoping for a much more convincing win in the coming weeks, when a crucial pivotal trial of the company’s lead asset, roluperidone in schizophrenia, is due to read out.
|Minerva's late-stage pipeline|
|Product||Mechanism of Action||Trial details|
|Roluperidone (MIN-101)||5-HT2A receptor antagonist; Sigma-2 opioid receptor agonist||Phase III schizophrenia trial ongoing (NCT03397134)|
|Seltorexant (MIN-202)||Orexin 2 receptor antagonist||Three phase IIb trials ongoing. MDD dose finding (NCT03227224); insomnia (NCT03375203); MDD vs Seroquel (NCT03321526).|
|MIN-117||5-HT1A & 5-HT2A receptor antagonist; Alpha-1 & Alpha-2 adrenoceptor agonist.||Phase II MDD trial ongoing (NCT03446846)|
|MDD = major depressive disorder. Source: EvaluatePharma.|