Somaxon Pharmaceuticals Presents Analyses of Silenor Clinical Data at the American Psychiatric Association Annual Meeting

Update: Silenor Now FDA Approved - March 17, 2010

Four poster presentations highlight data from the clinical development program of Silenor® (doxepin) for the treatment of insomnia

SAN DIEGO--(BUSINESS WIRE)--May 20, 2009 - Somaxon Pharmaceuticals, Inc. (Nasdaq: SOMX), a specialty pharmaceutical company focused on the in-licensing, development and commercialization of proprietary branded pharmaceutical products and late-stage product candidates for the treatment of diseases and disorders in the central nervous system therapeutic area, announced that data from four Phase 3 clinical trials of the company's product candidate Silenor® (doxepin) for the treatment of insomnia were presented today at the American Psychiatric Association (APA) 2009 annual meeting in San Francisco.

The four posters represent a subset of the data from Somaxon's completed clinical development program, which comprised four Phase 3 clinical trials evaluating Silenor, a low-dose formulation of doxepin for the treatment of insomnia. Three of the posters illustrate the robust sleep maintenance efficacy demonstrated by Silenor based upon objective clinical measures, together with the findings that such sleep maintenance efficacy was generally not accompanied by next-day residual sedation or decreased nighttime arousability, which findings may be related to Silenor's selective histamine (H1) antagonism. The fourth poster reviews Silenor's sleep onset efficacy data across all four Phase 3 clinical trials.

A summary of the scientific information presented today at the APA annual meeting is as follows:

Effects of Doxepin 1 mg and 3 mg on Early Morning Awakenings in Elderly Adults with Primary Insomnia

This analysis examined the impact of doxepin 1 mg and 3 mg on early morning awakenings in an elderly population with primary insomnia.

In this randomized, double-blind, placebo-controlled study of elderly adults, doxepin 1 mg and 3 mg demonstrated statistically significant improvements compared with placebo on the first night in sleep efficiency (SE) in the last third-of-the-night, SE in the last quarter-of-the-night and SE in hours 7 and 8. These improvements were generally sustained at night 85, which was the last night of the trial, with significance maintained for 3 mg on all endpoints except SE in Hour 8.

Next-day residual effects were assessed using the Digit Symbol Substitution Test (DSST), Symbol Copying Test (SCT), and a Visual Analog Scale (VAS) for sleepiness. There were no significant group differences in the DSST, SCT, or VAS at any timepoint during the trial. In addition, the overall incidence of adverse events was lower for the doxepin-treated groups than for the placebo-treated group in this trial.

The efficacy in preventing early morning awakenings without next-day residual effects in this study is notable, given that this symptom of insomnia is prevalent but seldom addressed in clinical trials.

Can an Insomnia Therapy Treat Sleep Maintenance Insomnia without Suppressing Arousability? Effects of Doxepin 1 mg, 3 mg, and 6 mg across Phase 3 Trials

This report reviewed the sleep maintenance efficacy from three randomized, double-blind, placebo-controlled Phase 3 clinical trials evaluating doxepin in adult and elderly populations with either primary or transient insomnia.

In each of these clinical trials, each dose of doxepin studied (1 mg, 3 mg and/or 6 mg) demonstrated statistically significant improvements in wake after sleep onset (WASO) on night one. In addition, wake time improvements occurred in most hours of the night for doxepin 3 mg and 6 mg. These significant improvements were maintained at the final timepoints for the two long-term trials included in the analysis.

These improvements in sleep maintenance parameters were not accompanied by statistically significant decreases in the number of awakenings (NAW) compared to placebo at any dose or time point in any trial, an interesting finding that is inconsistent with the existing literature involving currently-approved hypnotic medications. These results suggest that doxepin 1 mg, 3 mg and 6 mg may reduce time spent awake after nighttime arousals without suppressing arousability.

Effects of Doxepin 1 mg, 3 mg and 6 mg on Sleep Efficiency by Hour from Two Long-term Trials of Chronic Insomnia

This analysis examined time spent asleep by hour and residual effects data from two long-term, randomized, double-blind, placebo-controlled clinical trials evaluating doxepin in adult and elderly populations with chronic insomnia.

In both trials, each dose of doxepin studied (1 mg, 3 mg and/or 6 mg) significantly improved overall total sleep time (TST) on night one compared with placebo. In addition, sleep time by hour was significantly improved in the majority of hours throughout the night. These improvements were generally sustained at the final time point, with significance maintained for most parameters.

In terms of next-day residual effects, there were no significant differences in the DSST or SCT at any dose in either trial. All doses were well-tolerated, with no reports of complex sleep behaviors, amnesia or anticholinergic effects.

These data indicate that adult and elderly patients taking doxepin at doses of 1 mg, 3 mg, and 6 mg may experience an increase in time spent asleep that lasts throughout the night without evidence of next-day residual sedation. The results suggest that the efficacy of doxepin at low doses may be due in part to doxepin's selectivity for the histamine H1 receptor, and further suggest that histamine may be an integral part of a gating mechanism in the arousal system that allows transition from sleep to wake without residual sedation.

Night 1/Week 1 Effects of Doxepin 1 mg, 3 mg, and 6 mg on Sleep Onset Across Phase 3 Trials of Transient and Chronic Insomnia

This report reviewed sleep onset efficacy from four randomized, double-blind, placebo-controlled Phase 3 clinical trials evaluating doxepin in adult and elderly populations with either primary or transient insomnia.

Across these clinical trials, doxepin 3 mg and 6 mg significantly improved the majority of objective and subjective sleep onset parameters at the first assessed time point (night 1 or week 1). Statistical significance was generally not observed at later time points in these clinical trials.

These data suggest that doxepin 3mg and 6 mg can be effective at treating insomnia characterized by sleep onset difficulty in both transient and chronic insomnia populations, in both adult and elderly patient populations.

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:


  • 54% experience insomnia symptoms every night or a few nights a week,
     
  • 32% awake often during the night (sleep maintenance),
     
  • 21% wake up too early and cannot get back to sleep (premature final awakening), and
     
  • 21% have difficulty falling asleep (sleep onset).
     

Studies estimate that 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 (‰¤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.

On February 25, 2009, Somaxon received a Complete Response Letter from the FDA relating to its NDA for Silenor for the treatment of insomnia. In the Complete Response Letter, the FDA raised a number of issues relating to the interpretation of the efficacy data contained in the NDA and indicated that the FDA was open to a discussion of these concerns. With respect to safety, the FDA noted that there were no adverse events observed that would preclude approval, but asked the company to address the possibility that doxepin may prolong the cardiac QT interval.

Somaxon held a meeting with the FDA on April 6, 2009 to discuss the issues raised in the Complete Response Letter. Based on the feedback it received at the meeting, Somaxon is conducting additional analyses of its clinical data focused on the durability of subjective sleep maintenance efficacy in adults with primary insomnia. The company will complete these analyses during the second quarter of 2009 and will include them in a resubmission to the FDA. The FDA has indicated that the review cycle for such resubmission will be six months from the date of the resubmission.

Based on the Complete Response Letter and its meeting with the FDA, Somaxon will no longer pursue approval of a 1 mg dose of Silenor, nor will it seek approval of a statement in the indication section of the label that clinical trials of Silenor have demonstrated improvement in sleep onset.

About Somaxon Pharmaceuticals, Inc.

Headquartered in San Diego, CA, Somaxon Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the in-licensing, development and commercialization of proprietary branded pharmaceutical products and late-stage product candidates for the treatment of diseases and disorders in the central nervous system therapeutic area. Somaxon has submitted a New Drug Application for its product candidate, Silenor® (doxepin) to the U.S. Food and Drug Administration.

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 review process and the potential approval of the NDA for Silenor, and the scope of any such approval, 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, Somaxon's interpretation of its communications and interactions with the FDA relating to the requirements for approval of the NDA for Silenor, and the FDA's agreement with such interpretation; Somaxon's interpretation of the results of the clinical trials for Silenor, the timing of the interpretation of such results and the FDA's agreement with such interpretation; the potential for Somaxon to make a resubmission to the Silenor NDA; 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; Somaxon's ability to raise sufficient capital to meet FDA requirements and otherwise fund its operations, and to meet its obligations to parties with whom it contracts relating to financing activity; the impact of any such financing activity on the level of Somaxon's stock price; the impact of any inability to raise sufficient capital to fund ongoing operations, including the potential to be required to restructure the company or to be unable to continue as a going concern; Somaxon's ability to successfully commercialize Silenor, if it is approved by the FDA; 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; inadequate therapeutic efficacy or unexpected adverse side effects 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 treatments, and Somaxon's ability to compete within that market; 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 press 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.

Contact: PondelWilkinson, Inc.
Rob Whetstone, (310) 279-5963

Posted: May 2009

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