BARCELONA – An investigational antidepressant known for now simply as MIN-117 shows the potential – at least, in phase 2 development – of offering significant advantages over currently available antidepressants in patients with major depressive disorder, Michael Davidson, MD, said at the annual congress of the European College of Neuropsychopharmacology.
“This is a compound with a very, very rich pharmacology – so rich that we don’t know exactly which of the pharmacologic effects are really making the difference. This rich pharmacology is related to pathways that may confer toa unique positioning in the field of antidepressants and address unmet medical needs not well covered by existing therapies. For example, faster onset of action, complete restoration of euthymia, and beneficial effects on cognition and sexual functioning,” according to , chief medical officer at Minerva Neurosciences, which is developing the drug..
In the completed phase 2 study, the drug also displayed a strong anxiolytic effect and no prolongation of REM sleep latency in polysomnographic testing.
“So it may be that this is the first antidepressant which does not affect sleep architecture,” observed Dr. Davidson, professor of psychiatry at the Sackler School of Medicine in Tel Aviv.
Preclinical studies established that MIN-117 has high affinity for the 5HT serotonin transporter, serotonin 1A and 2A receptors, the dopamine transporter, and the alpha-1A and -1B adrenergic receptors. In animal models of depression, the drug results in sustained release of dopamine and serotonin. In human studies, the drug has a long half-life of roughly 60 hours.
“One possibility is that MIN-117 will be administered not once a day, but once or twice a week. It may be that here we have an antidepressant that doesn’t have to be administered every day,” the psychiatrist said.
In the completed phase 2 study, however, the drug was given once daily in what he described as a “classic design” for an antidepressant clinical trial: a 4-week washout period, then 6 weeks of double-blind treatment with MIN-117 at 2.5 or 0.5 mg/day, paroxetine at 20 mg/day, or placebo, then a 2-week posttreatment follow-up phase.
In describing the results of the study of 84 patients with major depressive disorder, Dr. Davidson painted a picture of MIN-117’s safety and efficacy with broad strokes because the trial wasn’t powered to demonstrate statistically significant differences. But the treatment effect sizes for the novel drug were impressive. A much more complete picture of the safety and efficacy of MIN-117 will be provided by an ongoing 324-patient phase 2b multicenter U.S. and European trial of the drug given at 2.5 or 5 mg/day or placebo.
The primary endpoint in the completed trial was change from baseline to 6 weeks in mean Montgomery-Åsberg Rating Depression Scale () score. From a baseline score of about 33, MADRS scores improved by 9 points with placebo, 11 with MIN-117 at 0.5 mg, and by 12 points with 2.5 mg of the drug. MIN-117 was superior to placebo in this regard from the time of the earliest assessment, at 2 weeks.
One-quarter of patients on MIN-117 at 2.5 mg/day achieved remission, prospectively defined as a MADRS score below 12. Remission was 2.1-fold more likely in this group than with placebo at week 4 and 3.1-fold more likely at 6 weeks. The remission rate with MIN-117 also was better than with paroxetine.
“So, and that we’ll be able to produce full remission of the depressive symptoms,” Dr. Davidson said.
MIN-117 also showed a solid anxiolytic effect, with mean scores on the– a secondary endpoint – improving by 10 points in both the 0.5- and 2.5-mg groups from a baseline of 26 points. As a result of this impressive showing, the large ongoing phase 2b study is recruiting patients with an ongoing episode of major depressive disorder and prominent secondary anxiety.
Both doses of MIN-117 were well tolerated. Scores on theshowed that the drug did not result in any impairment of sexual function. Nor was MIN-117 associated with evidence of cognitive impairment; in fact, scores on the Digit-Symbol Substitution Test and Digit Span Backwards tool were better than in the placebo arm.
The study was sponsored by Minerva Neurosciences and presented by the company’s chief medical officer.