Somaxon Presents Pharmacological Data on Doxepin at the 21st European College of...

Somaxon Presents Pharmacological Data on Doxepin at the 21st European College of Neuropsychopharmacology Congress

Study confirms doxepin, the active ingredient in Silenor(R) for
the treatment of insomnia, as a potent and specific histamine
antagonist
SAN DIEGO--(Business Wire)--
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.

About Silenor

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.

Investors:
Somaxon Pharmaceuticals, Inc.
Meg McGilley
Chief Financial Officer
(858) 480-0402
or
PondelWilkinson, Inc.
Rob Whetstone
(310) 279-5963
or
Media:
Manning, Selvage & Lee
Anne de Schweinitz
(212) 468-3779

Copyright Business Wire 2008