Orexin Antagonist Helps Merck Get Some Sleep

Blogging time has been sparse and I am only now catching up on a post I started last week. But it is about an area I am interested in, so I will continue regardless of the point that it is not quite so timely as it was when I started typing.

I think it is fair to say that Merck have had a rough time of late what with Vioxx and other assorted adventures. I’d wager that some of their management are having a little trouble getting their 8 hours a night. So it was probably comforting to hear the news about their insomnia drug currently in clinical trials (piece here on Bloomberg).

Suvorexant is the drug, which works a little differently to the already established Ambien, which is a GABA agonist. GABA agonists work by putting you to sleep, whereas suvorexant is an orexin receptor antagonist, which works by counteracting wakefulness. In principle, this should lead to less side effects and a better mental state (less drowsiness) next day. Ambien also has problems of drug tolerance, dependence and other adverse CNS side effects. And indeed, suvorexant has met the Phase III study goals and should be in the final phase of getting approved. Though the field of sleep aids is rather crowded, this one might just have an edge in overall tolerance and less side effects.

It is not all plain sailing. The other player in the Orexin field is GSK. They co-developed a compound called almorexant from Swiss company Actelion and that failed in its clinical trial. They have another compound in phase II, SB-649,868, so they have not given up on it yet. More worrying is that almorexant was abandoned because of its side effect profile, which seems counter-intuitive to what everyone is saying about suvorexant.


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