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Silenor

Generic name: doxepin
Treatment for: Insomnia

Update: Silenor Now FDA Approved - March 17, 2010

Somaxon Pharmaceuticals Submits New Drug Application for Silenorfor the Treatment of Insomnia

SAN DIEGO--(BUSINESS WIRE)--Jan 31, 2008 - Somaxon Pharmaceuticals, Inc., 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 it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Silenor (doxepin hydrochloride). Somaxon is seeking marketing approval of Silenor for the treatment of insomnia.

Pursuant to Prescription Drug User Fee Act (PDUFA) guidelines, the FDA is expected to determine whether to accept the NDA for filing within 60 days, and to notify the company of its determination within fourteen days thereafter. If the NDA is accepted for filing, under the PDUFA guidelines it is expected that the FDA will complete its review and provide an action letter with respect to the NDA within 10 months following submission of the NDA, or in December 2008.

"The completion and submission of our NDA for Silenor represents a significant milestone for Somaxon," said David F. Hale, Somaxon's executive chairman and interim chief executive officer. "It is the culmination of a thorough development program that includes six well controlled clinical trials, all of which met their primary endpoints, and multiple non-clinical studies. We believe that the improvements in sleep onset, sleep maintenance and sleep duration and the favorable safety and tolerability profile demonstrated by our clinical development program are sufficient to support a determination by the FDA that Silenor can be approved for the treatment of insomnia. I would like to thank the team at Somaxon, as well as the many clinicians and experts who worked with us, for their efforts in the design and conduct of the Silenor development program and the preparation of this NDA for submission."

"Insomnia is a significant health concern in the United States. Millions of people are affected, many of whom remain undiagnosed and untreated by a physician," said Tom Roth, Ph.D., chief, division head, Sleep Disorders & Research Center, Henry Ford Hospital. "There is mounting evidence that untreated insomnia can lead to significant health consequences, including an increased risk of depression, obesity and cardiovascular disorders. If Silenor is approved by the FDA, it has the potential to provide clinicians and patients with a unique treatment option for insomnia."

Andrew Krystal, M.D., associate professor with tenure, Duke University School of Medicine and Director, Sleep Research Laboratory and Insomnia Program, Duke University, added, "Pharmacologically, low dose doxepin, the active ingredient in Silenor, is unique. It is thought that Silenor improves sleep by selectively blocking the wake-promoting neurotransmitter histamine, thereby decreasing the drive for wakefulness. This novel mechanism of action most likely explains the significant improvement in insomnia symptoms that was observed in controlled clinical trials without adverse effects such as amnesia, complex sleep behaviors or physical or psychological dependence."

About the Silenor NDA and Background of the Development Program

Somaxon submitted the NDA for Silenor under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, which allows the company to rely on published literature reports or the FDA's findings of safety and efficacy for other formulations of doxepin hydrochloride that have previously been approved by the FDA. The NDA was submitted in accordance with the FDA's Electronic Common Technical Document (eCTD) specifications.

The NDA includes all of the data from the company's clinical development program, including data from each of Somaxon's four Phase 3 clinical trials evaluating Silenor for the treatment of insomnia. The following summarizes the results from these Phase 3 clinical trials:

The NDA submission also includes data from Somaxon's non-clinical development program, including the genotoxicity, reproductive toxicology and 26-week transgenic mouse carcinogenicity non-clinical studies of Silenor, which were initiated and completed based on a request from the FDA in May 2006. At that time, the FDA indicated that the data from the genotoxicity studies and reproductive toxicology studies should be included in the initial NDA submission. The FDA also indicated that depending on the outcome of the genotoxicity studies, it may be flexible as to the timing of the conduct of the requested carcinogenicity studies, including the potential that the data from those studies may be submitted as a post-NDA approval commitment.

In September 2006, Somaxon completed the genotoxicity studies, and no signal indicative of genotoxicity was found in any of the assays. The company submitted the results to the FDA, and the FDA agreed with the company's assessment that Silenor does not appear to have genotoxic potential. In February 2007, the FDA indicated that, unless other non-clinical data raise a concern, a complete assessment of the carcinogenic potential of Silenor may not be needed prior to NDA approval. The FDA also indicated that it may accept the results of a shorter-term carcinogenicity study for approval of the NDA and allow the standard two-year carcinogenicity study to be completed as a post-NDA approval commitment.

In May 2007, Somaxon received correspondence from the FDA which stated that the results of its 26-week transgenic mouse carcinogenicity study of Silenor should be included as part of the initial NDA submission for Silenor. The company continues to plan to submit the results of the standard two-year carcinogenicity study as a post-approval commitment. Somaxon initiated that study, which is a two-year carcinogenicity study in rats, in August 2007.

About Insomnia

Approximately 70 million American adults are affected by insomnia - characterized by difficulty falling asleep, waking frequently during the night, waking too early and not being able to return to sleep, or waking up not feeling refreshed.

Results from a 2005 National Sleep Foundation Sleep in America poll reported that respondents experienced the following insomnia symptoms:

An estimated 20% to 40% of all adults complain of acute, or transient, insomnia, generally defined as a complaint lasting several days up to a couple of weeks, while 10% to 15% complain of chronic insomnia, generally defined as a complaint lasting approximately four weeks or longer.

The negative health consequences of insomnia are becoming better understood. Studies have shown that insomnia lasting more than four weeks is associated with a wide range of adverse conditions, including mood disturbances, depression, difficulties with concentration and memory, and certain cardiovascular, pulmonary and gastrointestinal disorders. Chronic sleep deprivation has also been associated with an increased risk of diabetes and obesity. One study showed that when normal sleep was restricted by as little as two hours per night across two weeks, the affected person experienced a significant decrease in cognitive function that resulted in reaction time and other performance measures resembling those of a person who stayed up for 48 hours straight.

About Silenor

Silenor is a low-dose (1 mg, 3 mg, 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.

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 acceptance for filing or approval of the NDA for Silenor, the interpretation of the results of Somaxon's non-clinical studies and the FDA's agreement therewith, and the FDA's agreement that Somaxon may complete and submit the results of its two-year carcinogenicity study of Silenor as a post-approval commitment 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 the FDA to require non-clinical, clinical or other requirements to support acceptance for filing of the NDA for Silenor, or the imposition of additional requirements to be completed before or after regulatory approval; Somaxon's ability to demonstrate to the satisfaction of the FDA that potential NDA approval of Silenor is appropriate without standard, long-term carcinogenicity studies, given the context of completed trials and pending studies; the potential for Silenor to receive regulatory approval for one or more indications and with a label that is consistent with Somaxon's patent protection on a timely basis or at all; the timing and results of non-clinical studies for Silenor, and the FDA's agreement with Somaxon's interpretation of such results; 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; Somaxon's ability to have such patent protection provide exclusivity for Silenor; Somaxon's ability to operate its business without infringing the intellectual property rights of others; unexpected findings relating to Silenor that could delay or prevent regulatory approval or commercialization, or that could result in recalls or product liability claims; other difficulties or delays in development, testing, manufacturing and marketing of and obtaining regulatory approval for Silenor; the market potential for insomnia, and Somaxon's ability to compete; Somaxon's ability to raise sufficient capital; 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.

Posted: January 2008

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