SILENOR™ (doxepin HCl tablets) - A Successful Clinical Development Program

On January 31, 2008, Somaxon submitted a New Drug Application (NDA) for SILENOR™ to the Food and Drug Administration (FDA). We have completed four Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trials designed to assess the efficacy and safety of SILENOR™ (doxepin HCl tablets) for the treatment of insomnia. In each of these clinical trials, SILENOR™ demonstrated statistically significant and clinically meaningful results in the designated primary endpoint and in several other important secondary endpoints. These endpoints included measures of both sleep maintenance and sleep onset. Specifically, we completed:

• A clinical trial of 229 adults with chronic insomnia that evaluated SILENOR™ in the sleep laboratory setting over a 35-day period. The primary endpoint of this trial was wake after sleep onset (WASO), a measure of sleep maintenance. Statistical significance vs. placebo for the primary endpoint was achieved with a p-value of <0.0001.  In addition, multiple objective and subjective secondary endpoints also achieved statistical significance.

• A clinical trial of 565 healthy adults experiencing transient insomnia that evaluated SILENOR™ in the sleep laboratory setting. This clinical trial utilized a validated phase advance model that evaluated induced insomnia over one night. The primary endpoint was latency to persistent sleep (LPS), a measure of sleep onset. Statistical significance vs. placebo for the primary endpoint was achieved with a p-value of <0.0001. Multiple secondary endpoints also achieved statistical significance.

• A clinical trial of 255 elderly patients with primary sleep maintenance insomnia that evaluated SILENOR™ in an outpatient setting over a four-week period. Patient-reported, or subjective, total sleep time (sTST), a measure of sleep duration, was the primary endpoint. Statistical significance vs. placebo for the primary endpoint was achieved with a p-value of <0.0001. Multiple secondary endpoints, including patient evaluations suggesting improvement in time to fall asleep, also achieved statistical significance.

• A clinical trial of 240 elderly patients with chronic primary insomnia that evaluated SILENOR™ in both the sleep laboratory and an outpatient setting over a three-month period. This is, to the best of our knowledge, the longest trial evaluating the efficacy of a treatment of insomnia in both the sleep laboratory and outpatient settings in elderly patients. In this trial, the primary endpoint of WASO was statistically significant vs. placebo for both doses studied (1 mg: p=0.0053, 3 mg: p<0.0001), as were multiple secondary endpoints. Like our other SILENOR™ trial in the elderly, both clinicians and patients in the SILENOR™ group rated marked improvement in insomnia symptoms over time.