Transcept Pharmaceuticals Issues Update On Intermezzo Regulatory Review

Transcept Pharmaceuticals submitted a revised proposal for the resubmission of the Intermezzo New Drug Application (NDA) to the FDA for evaluation and comment. 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 agency 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.

In addition, the FDA identified that the Intermezzo data submitted by Transcept did not demonstrate next day residual effects significantly different from placebo. The agency 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 agency expressed two concerns in concern to 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.

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. The agency indicated that the revised packaging appeared to reduce the potential for inadvertently taking more than one dose in a single night.

The FDA, however, 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.

Transcept, as requested by the FDA, 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.

Transcept has also 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.

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 the company.

Glenn Oclassen, president and CEO of Transcept, said: “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.”