WALTHAM, Mass.—Minerva Neurosciences Inc. achieved positive top-line results in a Phase 1b clinical trial in major depressive disorder (MDD) with MIN-202 (JNJ-42847922). The selective orexin-2 receptor antagonist is under joint development between Minerva and Janssen Pharmaceutica NV. A clinical-stage biopharmaceutical company that develops therapies for central nervous system (CNS) disorders, Minerva’s proprietary compounds include: MIN-101, in Phase 2b development for schizophrenia; MIN-202 (JNJ-42847922), in Phase 2a and Phase 1b development for insomnia and adjunctive treatment of MDD, respectively; MIN-117, in Phase 2a development for MDD; and MIN-301, in preclinical development for Parkinson’s disease.
According to Dr. Remy Luthringer, president and CEO of Minerva, “Treatment with MIN-202 was observed to result in consistent improvements in the symptoms of depression in MDD patients in this trial. The results pave the way to initiate a Phase 2b trial in patients suffering from MDD. These improvements support the potential of MIN-202 to have a direct effect on mood independent from its effect on sleep. We previously observed that MIN-202 had a significant effect on sleep in our Phase 2a trial in patients suffering from insomnia disorder.”
MIN-202 seeks to inhibit the activity of the neurons that promote wakefulness by selectively blocking the orexin 2 receptor. The orexin system is involved in the control of several key functions, including metabolism and wakefulness. Blocking the orexin 2 receptor reduces the level of neurotransmitter traffic that signals the brain to maintain vigilance and wakefulness, which can be helpful for patients with insomnia. This is a completely different mechanism from products that work as GABA (gamma-aminobutyric acid) agonists, which induce sleep via sedation.
Minerva entered into a co-development and license agreement with Janssen in February 2014 that covered MIN-202 and any other orexin 2 compounds. Under this agreement, Minerva has an exclusive license to these compounds in the European Union, Switzerland, Liechtenstein, Iceland and Norway, while Janssen has exclusive rights to these compounds worldwide outside of those territories. During its 2015 Pharmaceutical Pipeline update, Janssen reported that it plans to file the insomnia disorder indication by 2019.
According to the company, the Phase 1b trial was a randomized, multi-center, double-blind, parallel group, diphenhydramine- and placebo-controlled study to evaluate the effect of MIN-202 in MDD outpatients 18 to 65 years of age. Forty-eight participants were enrolled in three groups that received doses of 20 mg of MIN-202 daily, 25 mg of diphenhydramine daily (used as a positive control to induce sedation) or placebo over four weeks. MIN-202 was well tolerated by study participants over a one-month treatment period, with no new safety problems or adverse events.
There were consistently greater improvements in depressive symptomatology in patients randomized to receive MIN-202, as compared with those randomized to receive placebo or diphenhydramine. These were measured by clinician-administered rating scales, including the Hamilton Depression Rating Scale (HDRS17). Core symptoms of depression (as measured by the HAM-D6) were significantly improved in the MIN-202 arm when compared with the placebo arm.
The primary endpoint was safety and tolerability, and secondary endpoints included assessments of depressive symptomatology, cognition and sleep. The trial was conducted at seven clinical sites in Europe.
MIN-202 is also under development to treat primary insomnia disorder. Top-line data from a Phase 2a trial in this indication included statistically significant improvements in sleep efficiency as measured by objective polysomnography, the primary endpoint of the trial. This was observed in study patients treated with MIN-202, with an acceptable safety and tolerability profile, compared to patients treated with placebo.
“It is premature to discuss the commercial potential of this product,” Luthringer commented. “Such potential will be defined significantly by data from advanced clinical trials in insomnia disorder and mood disorders.”