Somaxon Pharmaceuticals Nearing End of FDA Fatigue for Silenor?

Last Updated Jan 22, 2010 10:11 AM EST

Somaxon Pharmaceuticals said the U.S. Food and Drug Administration accepted the resubmission of the new drug application for Silenor (doxepin), its investigational treatment for insomnia, as a complete Class 1 response. Although not an approvable action letter, this move does signal receptiveness by health regulators to complete the drug review within a 60-day period.

As companies -- including Somaxon (NASDQ:SOMX) -- do not disclose contents of complete-response letters, it is difficult to interpret the material intentions of the FDA. Nonetheless, Class 1 resubmissions typically address just small deficiencies in the application, such as labeling or a minor re-analysis of previously submitted data to the application, according to Center for Drug Evaluation and Research procedures.

Understandably, chief executive Richard Pascoe could not discuss with me anything beyond what was stated in the press release. That said, he did confirm that regulators did not raise any new issues or concerns. In my opinion, both parties will likely go one more round -- wrangling over a minor efficacy endpoint (in my opinion): the robustness of sustained subjective sleep maintenance efficacy in non-elderly adults with primary insomnia.

Commenting on the pharmacological management of insomnia (Drug Benefit Trends. 2009;21:266-271) Dr. David N. Neubauer, associate director of the Johns Hopkins Sleep Disorders Center, wrote:

The challenge for the future will continue to be the optimization of efficacy and safety in the promotion of nighttime sleep and daytime functioning. Improvement in the quality of life for insomnia sufferers must be the ultimate goal.
Looking to cut through all the regulatory ambiguities, I asked Dr. Neubauer to opine on the potential merits of Silenor as a drug treatment for insomnia:
None of us are privy to the FDA communications with Somaxon, so we can only speculate.... The low-dose doxepin studies generally have demonstrated reasonable efficacy, particularly for sleep maintenence (and uniquely for the final 1/3 of the night). Although there are well-known safety concerns with doxepin at standard doses, the very low Silenor doses should be very safe. At these doses the main pharmacodynamic activity should only be the desired sedating antihistamine effect. While a doxepin overdose could be fatal, it would be hard to do with 3 and 6 mg pills. There should be no abuse potential, since this does not exist at higher dose.

Rebound insomnia should not occur, but even if it did that shouldn't be a major problem as most of the currently approved insomnia medications have some degree of rebound insomnia. I don't believe that Silenor was associated with any significant degree of next-day fatigue or sleepiness.

Somaxon, which received a second complete-response letter from FDA in December, anticipates a decision from the FDA by March 21, 2010.

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  • David Phillips

    David Phillips has more than 25 years' experience on Wall Street, first as a financial consultant and then as an equity analyst for several investment banking firms. He sifts through SEC filings for his blog The 10Q Detective, looking for financial statement soft spots, such as depreciation policies, warranty reserves and restructuring charges. He has been widely quoted in outlets such as BusinessWeek, The International Herald Tribune, Investor's Business Daily, Kiplinger's Personal Finance, and The Wall Street Journal.