Somaxon and Silenor, A Win-Lose Situation?

Implications: The NDA submission of Somaxon’s Silenor, a reformulation of the tricyclic antidepressant doxepin at very low doses, for the treatment of insomnia is not particularly compelling news clinically.  Low doses of doxepin provide an anti-histamine effect with less norepinephrine or serotonin reuptake properties, the basis of its antidepressant effect.   At first glance, this would not be a drug to have wide clinical or commercial value – perhaps an expensive version of diphenhydramine (Benardryl) or hyroxyzine (Vistaril).  But that doesn’t necessarily mean bad news for Somaxon….

Analysis: An FDA indication for insomnia with good marketing would still not likely make this drug anything of a winner in the insomnia market, much less a blockbuster.  Its clinical value and comparative side effect profile would need to be seen but even if favorable, market perception of the drug seems to be starting at a distinct negative.  And there are many good FDA-indicated treatments for insomnia, including generic zolpidem (Ambien), as well as frequent off-label uses of drugs with better market perception and clinican comfort than doxepin.    

However, I doubt Somaxon’s goal is to introduce a big winner here.  Even a small sliver of the insomnia population could grant them a relative victory.  By filing the NDA via a 505(b)(2) route, they are able to demonstrate safety based on prior data for doxepin and have their Phase III trials and results without the associated development costs and burdens.  Safety is an increasingly bigger issue for investigational new drugs and the risk is obviously hedged here with a drug used clinically.  An FDA indication with formulary coverage for the branded drug could create a financial base for Somaxon’s pipeline, which appears more attractive than Silenor itself.  Market exclusivity would protect the product for 5 years, patent and related regulatory protections would add some additional time, though I suspect prescribing of the generic 10 mg form of doxepin would occur if, by some measure, Silenor actually picked up steam.  All said, I think Somaxon’s strategy here may be better off than Silenor’s prospects.