FDA has issued Transcept Pharmaceuticals a second complete response letter (CRL) saying it still can’t approve the firm’s resubmitted NDA for the sleep-aiding drug Intermezzo® (zolpidem tartrate sublingual tablet), due to potential safety issues. Transcept says it plans to meet with the agency to discuss how to move forward and address the stated concerns.
Intermezzo has been developed for use by patients when they wake and can’t get back to sleep in the middle-of-the-night, and is not supposed to be used by patients less than four hours before they are due to get up. The drug would be packaged as a single-dose unit, which FDA reportedly is happy would adequately address the risk of inadvertent re-dosing.
However, the agency is still worried that some patients will take the drug when they have less than four hours remaining in bed. The latest CRL also stated that during its review of clinical data provided by Transcept to address the original October 2009 CRL, it became concerned that patients with higher zolpidem blood levels due to misdosing could be at risk of next-day impairments in driving ability. The studies reviewed included an FDA-agreed highway driving study.
As a possible way forward FDA has suggested Transcept further investigate whether body weight and other demographic factors could contribute to differentially elevated blood levels the morning after dosing with Intermezzo, and develop strategies to decrease next-morning blood levels of the drug. After implementing mitigation strategies the firm would then need to demonstrate that Intermezzo doesn’t present an unacceptable risk of impairment the morning after dosing. This may include conducting an additional driving study.
Intermezzo is Transcept’s lead pipeline candidate and is being developed for the U.S. market in collaboration with Purdue Pharmaceutical. The sublingual low-dose zolpidem formulation contains a quarter to a third of the active dose contained in currently marketed zolpidem-based sleep aids.