Minerva Neurosciences reports positive phase I data with MIN-202

Preliminary results from two additional Phase 1 studies also suggest that MIN-202 is well tolerated and possesses advantageous pharmacokinetic and pharmacodynamic features.

The three Phase 1 studies were conducted by Janssen Research & Development, LLC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, as part of a collaboration to develop MIN-202 with Minerva that was facilitated by Johnson & Johnson Innovation Ltd in London.

"Treatment of sleep disorders remains a significant challenge in patients with both primary insomnia and many CNS diseases. These positive data indicate that MIN-202 could be an effective treatment able to both induce and maintain sleep," said Remy Luthringer, PhD, president and CEO of Minerva, adding "With these findings we have identified a dose range to advance this compound."

In patients with mood disorders, sleep disturbances (both insomnia and hypersomnia) have been associated with a suboptimal response to antidepressant drug (AD) therapy, an increased risk for relapse (in AD-responsive patients), and prodromal depression. Recent studies have shown that orexin-2 receptor antagonism might have a beneficial effect on overall arousal and stress level.

"We are especially encouraged by findings that support the use of MIN-202 in the treatment of both primary insomnia as well as sleep disorders associated with MDD," Dr. Luthringer added.

This was a double-blind, placebo-controlled, randomized, four-way crossover, single dose study in 20 male and female patients with MDD and insomnia. The primary endpoint was the effect of MIN-202 (dosed PM) on latency to persistent sleep (LPS).

Some additional endpoints were evaluated by PSG (polysomnography). Preliminary results demonstrated a statistically significant effect on LPS in all three doses tested (10, 20, and 40 mg). Treatment with MIN-202 also resulted in prolonged total sleep duration by approximately 45 minutes.

This was a double-blind, placebo-controlled, randomized MAD study in sequential cohorts of healthy males and females. MIN-202 was administered in the morning at dose levels ranging from 5mg to 60mg for 10 days. A dose level as low as 5mg was shown to elicit sedation while dose levels >= 20mg induced (daytime) somnolence. MIN-202 plasma exposure was dose proportional from 5mg to 20mg. At higher doses, the exposure was less than dose proportional.

The two studies described above were carried out using a suspension formulation of MIN-202. This third study evaluated treatment with a solid dose formulation of MIN-202 to potentially support additional clinical studies. In this study, similar pharmacokinetic profiles were observed for both formulations, qualifying the solid dose to support further clinical studies.

In these Phase 1 studies, MIN-202 was found to be generally well tolerated.

MIN-202 is an orexin-2 (OX) antagonist being developed by Minerva Neurosciences in collaboration with Janssen Pharmaceutica NV, for the treatment of sleep disorders. The most commonly available medications to treat insomnia are GABA-mimetics (e.g., Ambien), which activate sleep-promoting neurons.

During the last decade, the critical role of the orexin system in maintaining wakefulness in humans has been confirmed. Promoting sleep by inhibiting the OX-2 receptor may hold the promise of improved safety (decreased interactions with other CNS functions), better restoration of natural sleep architecture (structure and pattern of sleep), and improved continuity (amount and distribution of sleep versus wakefulness), potentially leading to improvements in sleep quality and next day functioning.