September 2, 2008
Somaxon Presents Pharmacological Data on Doxepin at the 21st European College of Neuropsychopharmacology Congress
Somaxon Pharmaceuticals, Inc. (Nasdaq:SOMX), a specialty pharmaceutical company focused on the in-licensing and development of proprietary product candidates for the treatment of diseases and disorders in the fields of psychiatry and neurology, today announced that data from a pharmacological profiling study relating to doxepin, the active ingredient in the company's product candidate Silenor for the treatment of insomnia, were presented yesterday at the 21st European College of Neuropsychopharmacology (ECNP) Congress.
The data presented at the ECNP Congress are from a study that examined the in vitro pharmacological profile of doxepin. The study evaluated the relative affinity and functional activity of doxepin at various central nervous system (CNS) targets known to play a role in its overall pharmacological profile.The results demonstrate that doxepin has high affinity for and potent antagonistic activity at the human H1 histamine receptor, which is thought to be a primary mediator of the sleep-wake cycle. In addition, doxepin was shown to have lower or little affinity for a number of other CNS binding sites.
It is hypothesized that at the point in the circadian cycle during which the release of histamine and wakefulness are both naturally reduced, blocking the H1 receptor can further reduce wakefulness and promote the initiation and maintenance of sleep. The high potency of doxepin as an H1 antagonist represents the likely mechanism for its sleep-promoting effects and provides a potential explanation for its efficacy in humans at oral doses of 1 mg, 3 mg and 6 mg, the doses evaluated in the company's clinical trials of Silenor for the treatment of insomnia. In addition, the relative selectivity of doxepin for H1 as compared to a number of other neuropharmacological sites may account for the low incidence in such clinical trials of adverse events that have been associated with higher doses (25 mg to 50 mg) of doxepin.
"When the dose of doxepin is lowered to the 1-6 mg range, the clinical profile appears to be consistent with that of a selective H1 antagonist," said Philip Jochelson, M.D., Somaxon's Senior Vice President and Chief Medical Officer. "We believe that this selectivity may explain the clinical efficacy and safety profile of Silenor observed in our clinical development program for the treatment of insomnia. Specifically, in our controlled clinical trials of the 1 mg, 3 mg and 6 mg doses of doxepin contained in Silenor, improvements were demonstrated in measures of sleep onset, sleep maintenance and prevention of early awakenings, with no anticholinergic effects and no clinically meaningful next-day residual effects."
Somaxon's clinical trials for Silenor also demonstrated a low dropout rate and no evidence of amnesia, complex sleep behaviors, hallucinations, tolerance or withdrawal effects.
A summary of the poster presentation delivered at the ECNP annual meeting is as follows:
In Vitro Pharmacological Profile of Doxepin, a Sleep-Promoting Histamine H1 Antagonist
The study evaluated the affinity of doxepin at CNS targets known to play a role in its overall pharmacological profile. Functional assays were performed at selected sites of interest. Three comparison agents with established use in insomnia (trazodone, diphenhydramine and doxylamine) were also evaluated.
Doxepin was found to have high affinity and potency as an antagonist at the H1 receptor. Doxepin had measurable affinity for various adrenergic, muscarinic and serotonergic sites, but these affinities were substantially lower than for the H1 receptor.
Trazodone, an antidepressant frequently prescribed off-label for the treatment of insomnia, had low affinity for the H1 site. The antihistaminergic sleep aids diphenhydramine and doxylamine had relatively high affinity for the H1 site, but bound to muscarinic sites as well. Doxepin's superior margin of selectivity for H1 versus muscarinic M1 receptors may help explain the reduced incidence of anticholinergic side effects observed with Silenor compared with that of over-the-counter antihistamines used in insomnia, which typically contain diphenhydramine or doxylamine.
Silenor is a low-dose (1 mg, 3 mg and 6 mg) oral tablet formulation of doxepin hydrochloride that is patent protected for use in insomnia. Doxepin has been prescribed for more than 35 years for the treatment of depression and anxiety at dosages typically ranging from 75 mg to 300 mg per day. At these higher doses used for these indications, doxepin is known to have a range of undesirable side effects, including anticholinergic and next-day residual effects. However, based upon the controlled clinical trials of Silenor completed by Somaxon, the company believes that Silenor will be well tolerated by patients. In addition, the FDA has indicated that it will recommend that Silenor not be scheduled as a controlled substance.
About Somaxon Pharmaceuticals, Inc.
Headquartered in San Diego, CA, Somaxon Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the in-licensing and development of proprietary product candidates for the treatment of diseases and disorders in the fields of psychiatry and neurology. Somaxon has completed four successful Phase 3 clinical trials for its lead product candidate, Silenor (doxepin HCl) for the treatment of insomnia. The FDA has notified Somaxon that it accepted the NDA for Silenor for review as of March 31, 2008. Pursuant to PDUFA guidelines, Somaxon expects that the FDA will complete its review and provide an action letter to the company with respect to the NDA by December 1, 2008.
For more information, please visit the company's Web site at www.somaxon.com.
Somaxon cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. For example, statements regarding the potential approval of the NDA for Silenor and the interpretation of the results of Somaxon's clinical trials and non-clinical studies and the FDA's agreement therewith are forward looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Somaxon that any of its plans will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in Somaxon's business, including, without limitation: the potential for Silenor to receive regulatory approval for one or more indications on a timely basis or at all; the potential for the FDA to impose non-clinical, clinical or other requirements to be completed before or after regulatory approval of Silenor; Somaxon's ability to demonstrate to the satisfaction of the FDA that potential NDA approval of Silenor is appropriate prior to the completion of standard, long-term carcinogenicity studies, given the context of completed trials and pending studies; the timing and results of non-clinical studies for Silenor, and the FDA's agreement with Somaxon's interpretation of such results; unexpected findings relating to Silenor that could delay or prevent regulatory approval or commercialization, or that could result in recalls or product liability claims; the potential to enter into and the terms of any strategic transaction relating to Silenor; the scope, validity and duration of patent protection and other intellectual property rights for Silenor; whether any approved label for Silenor is sufficiently consistent with such patent protection to provide exclusivity for Silenor; Somaxon's ability to operate its business without infringing the intellectual property rights of others; other difficulties or delays in development, testing, manufacturing and marketing of and obtaining regulatory approval for Silenor; the market potential for insomnia treatments, and Somaxon's ability to compete within that market; Somaxon's ability to raise sufficient capital and meet its obligations to parties with whom it contracts relating to financing activity, and the impact of any such financing activity on the level of Somaxon's stock price; and other risks detailed in Somaxon's prior press releases as well as in its periodic filings with the Securities and Exchange Commission.
You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Somaxon undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934.