OncologySomaxon Resubmits New Drug Application For Silenor(R) (Doxepin) For The Treatment Of Insomnia
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, today announced that it has resubmitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Silenor® (doxepin) for the treatment of insomnia.
The resubmission includes additional statistical analyses of the company"s clinical data relating to the durability of subjective sleep maintenance efficacy. It also includes the results of the company"s completed clinical trial of doxepin that evaluated the potential for electrocardiogram, or ECG, effects. The results of that clinical trial demonstrated that Silenor had no effect on QT interval prolongation when administered at 6 mg or under exaggerated exposure conditions of 50 mg. The FDA has indicated that the review cycle for the resubmission will be six months.
"We believe that this resubmission fully addresses all of the issues raised in the Complete Response Letter that we received from the FDA on February 25, 2009 and further clarified in our meeting with the FDA on April 6," said Richard W. Pascoe, Somaxon"s president and chief executive officer. "We are confident that the additional clinical efficacy data analyses included in the resubmission demonstrate sustained subjective sleep maintenance efficacy in adults. Based on those analyses, as well as the favorable results from our ECG study, we believe that the resubmission can support a determination by the FDA that Silenor be approved for the treatment of insomnia."
"Silenor is highly differentiated from currently available insomnia treatments and has significant commercial potential, if it is approved by the FDA," continued Pascoe. "With this potential in mind, we intend to advance our current discussions relating to a commercial partnership for Silenor, with the goal of entering into an agreement that will maximize the commercial success of Silenor, if it is approved by the FDA. In addition, during June we intend to seek to raise cash in an amount sufficient to fund our operations at least through the FDA review period."
Silenor Regulatory Background
On February 25, 2009, Somaxon received a Complete Response Letter from the FDA relating to its NDA for Silenor for the treatment of insomnia. Based on its review, the FDA determined that the NDA could not be approved in its then-current form. In the Complete Response Letter, the FDA raised a number of issues relating to the interpretation of the efficacy data contained in the Silenor 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 responded by submitting to the FDA the results of its completed clinical trial of doxepin that evaluated the potential for ECG effects. The results of this clinical trial demonstrated that doxepin had no effect on QT interval prolongation when administered at 6 mg or under exaggerated exposure conditions of 50 mg.
Somaxon held a meeting with the FDA on April 6, 2009 to discuss the issues raised in the Complete Response Letter. In the meeting, the FDA stated that to obtain approval of a chronic insomnia treatment, objective and subjective efficacy must be established in adult and elderly patient populations, and efficacy must be shown both at the beginning of treatment and on a persistent basis, defined as at least one month. No additional safety issues were raised in the meeting, and the FDA has not requested that the company conduct additional clinical trials of Silenor.
Based on the feedback it received at the meeting, Somaxon conducted additional analyses of its clinical data, focusing on the durability of subjective sleep maintenance efficacy in adults with primary insomnia, and included them in its resubmission to the FDA.
In addition, 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.
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 that have previously been approved by the FDA. The NDA includes the data from Somaxon"s completed clinical development program for Silenor, which included six randomized, double-blind, placebo-controlled, multi-center clinical trials designed to assess the efficacy and safety of Silenor for the treatment of insomnia. All of the clinical trials demonstrated statistically significant differences relative to placebo on their primary endpoints and multiple secondary endpoints. Four of these were 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 studies of Silenor, which were undertaken based on a previous request from the FDA. The company continues to plan to submit the results of its standard two-year carcinogenicity study as a post-approval commitment. Somaxon initiated that study in August 2007 and expects data from the study in the first quarter of 2010.
Somaxon Pharmaceuticals, Inc.