October 28, 2009 Complete Response Letter
As previously announced, the FDA stated in the CRL that it believes Transcept has submitted substantial evidence of effectiveness for the use of Intermezzo® in the as-needed treatment of insomnia when a middle of the night awakening is followed by difficulty returning to sleep. However, the FDA indicated that the intended use of Intermezzo® in the middle of the night represents a unique insomnia indication and dosing strategy for which safety has not been previously established, and that the Intermezzo® NDA could not be approved in its present form.
The FDA further recognized that the Intermezzo® data submitted by Transcept did not indicate next day residual effects significantly different from placebo. However, the FDA requested additional data demonstrating that Intermezzo®, when taken as directed in the middle of the night, would not present an unacceptable risk of residual effects, with particular reference to next day driving ability.
The FDA expressed two concerns regarding the possibility of patient dosing errors in the middle of the night that could lead to next day residual effects, with particular reference to next day driving ability. Specifically, the FDA asked Transcept to address methods to avoid inadvertent dosing with less than four hours of bedtime remaining and inadvertent re-dosing in a single night.
Redesigned Packaging and Patient Instructions
In the briefing document submitted prior to the January 20, 2010 meeting, Transcept proposed a new Intermezzo® bedside unit-dose package and patient instructions designed to reduce the possibility of patient dosing errors. In the meeting minutes, the FDA indicated that the revised packaging appeared to reduce the potential for inadvertently taking more than one dose in a single night. However, the FDA expressed a remaining concern that the revised packaging may not adequately address the risk of dosing with less than four hours of time remaining in bed, with particular regard to the possibility of impaired driving.
Transcept and the FDA also reviewed the types of data that could support the evaluation of the proposed packaging and instructions, including data from pre-approval assessments of patient understanding of dosing instructions and a potential patient use study of the new Intermezzo® packaging. As requested by the FDA, Transcept has provided information on the challenges and limitations of pre-approval patient use studies, and has submitted a plan to assess and optimize patient understanding of the new packaging and patient instructions.
Intermezzo® Safety Profile Characterization
To further understand the safety of dosing Intermezzo® in the middle of the night, Transcept has proposed to the FDA to conduct a pre-approval highway driving study to assess the effect of Intermezzo® on driving ability beginning at approximately three hours and four hours post-dosing. Transcept has also submitted additional supportive analyses of data from a previously conducted Intermezzo® pharmacokinetic and pharmacodynamic study at time points up to four hours post-dosing. Results from this study were published in a 2008 article titled "Daytime pharmacodynamic and pharmacokinetic evaluation of low-dose sublingual transmucosal zolpidem hemitartrate" in the journal Human Psychopharmacology, an abstract of which is publicly available at www.interscience.wiley.com.
FDA Review of Transcept Post-Meeting Proposals
In the meeting on January 20, 2010, the FDA agreed to review the revised proposal for the Intermezzo® NDA resubmission and consider its adequacy to support the potential approval of Intermezzo®. The FDA has not set a date for the completion of its review of this proposal or the timing of its response to Transcept. Transcept plans to provide an update on the Intermezzo® development program, as appropriate, after it receives the results of the FDA's review of the revised proposal.
Glenn A. Oclassen, President and Chief Executive Officer of Transcept, commented, "We are encouraged by the progress made in our recent interactions with the FDA, and appreciate the FDA's willingness to engage in a collaborative dialogue in order to help define the steps necessary for us to resubmit the Intermezzo® NDA."
Transcept Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the development and commercialization of proprietary products that address important therapeutic needs in neuroscience. The most advanced Transcept product candidate is Intermezzo® (zolpidem tartrate sublingual tablet), for which a New Drug Application (NDA) was submitted to the U.S. Food and Drug Administration (FDA) in September 2008 seeking approval as a prescription sleep aid for use in the middle of the night at the time a patient awakens and has difficulty returning to sleep. In October 2009, Transcept received a Complete Response Letter from the FDA on the Intermezzo® NDA and is working to respond to issues raised in the letter. Transcept and Purdue Pharmaceutical Products, L.P. have entered into a collaboration agreement for the development and commercialization of Intermezzo® in the United States. For further information, please visit the company's website at: www.transcept.com.