Drug companies take years - even decades, and burn a tremendous amount of cash to bring a drug to the market. The process of drug development is challenging as the product candidate may fail in the clinical stage itself or may fail to pass the FDA muster after successfully completing all the stages of trials.
Only some companies, in spite of various setbacks, exude a steely determination and press on without quitting, and Transcept Pharmaceuticals Inc. (TSPT) is one among them. The company's sleep drug candidate Intermezzo, which was twice rejected by the FDA, will be at the altar again when its New Drug Application is resubmitted by the end of September 2011.
Read on to find out more about Transcept and its investigational sleep drug Intermezzo...
Intermezzo is designed to help insomnia sufferers return to sleep when they wake up in the middle of the night. Nocturnal awakening or middle-of-the-night awakening, followed by difficulty returning to sleep, is one form of sleep disorder.
A study conducted by the Stanford Sleep Epidemiology Research Center in 2008 in 9,000 individuals, found that about one-third of adults in the United States experience middle of the night awakenings at least three times each week. More than 90% of the subjects who experienced middle of the night awakenings reported that this insomnia symptom persisted for at least six months.
Middle of the night awakenings typically do not occur every night, and there is no FDA-approved sleep aid specifically for this sleep disorder.
The active ingredient in Intermezzo is zolpidem, the same as that found in well known prescription sleep aid Ambien and its generic version. Intermezzo , which contains the lowest dose of zolpidem, is designed as sublingual dosage form to rapidly deliver zolpidem to allow patients to return to sleep quickly.
Transcept initially filed its New Drug Application with the FDA seeking approval for Intermezzo in September 2008. The drug failed to clear the regulatory muster then as the FDA, which reviewed the Intermezzo NDA, issued a complete response letter in October 2009. The FDA sought additional data with particular reference to Intermezzo's impact on next day driving ability. In its complete response letter, the FDA also requested the company to address methods to lessen the risk if the patients take the drug when they have less than four hours of bedtime remaining or if they accidentally take more than the prescribed dose in a single night.
The company resubmitted its Intermezzo NDA, addressing the FDA concerns in January 2011. The Intermezzo NDA resubmission was considered as a complete Class 2 response by the FDA with a decision date set on July 14. However, the second time too proved unlucky for Transcept as it was issued a complete response letter by the FDA on July 14. While the FDA was satisfied with the efficacy of Intermezzo, concerns like safety profile and possible adverse effects of the drug on driving ability were again raised in the complete response letter.
Transcept met with the FDA on September 14 to discuss the regulatory path forward for Intermezzo. Following the meeting, Transcept plans to resubmit the NDA by the end of this month.
Transcept has proposed to reduce the recommended Intermezzo dose for women from 3.5 mg to 1.75 mg, and to keep the recommended Intermezzo dose for men at 3.5 mg. The company has also proposed new instructions stating that Intermezzo should only be taken if patients have at least 4 hours of bedtime remaining, and that patients should refrain from driving for at least 1 hour after arising and until 5 hours after dosing Intermezzo. The FDA has agreed to Transcept's proposals, and no additional studies are planned prior to resubmission of the Intermezzo NDA.
The resubmission will be considered as a two-month, Class 1 review by the FDA if the NDA is adequately concise.
The currently approved sleep aids like Ambien, Ambien CR, Lunesta, Restoril , Rozerem, Sonata , Desyrel and Silenor, are indicated for bedtime use only. If approved, Intermezzo will be the first sleep aid for use in the middle of the night at the time of awakening. The potential market of sleep aids to treat middle of the night awakenings is estimated to be worth $1.9 billion to $3.4 billion.
The development of sleep drugs is fraught with challenges and the path to approval has not been easy. In 2006, Indiplon developed by Neurocrine Biosciences (NBIX) failed to win FDA approval, following which the company ceased all clinical development activities in the U.S. related to that drug candidate. Silenor, another insomnia drug, developed by Somaxon Pharmaceuticals Inc. (SOMX) was finally able to make it to the pharmacy shelves only in March 2010 after being twice rejected in 2009.
Will Transcept resubmit a concise Intermezzo NDA by the end of this month and will the sleep drug successfully cross the regulatory finish line at least this time? Stay tuned...
For comments and feedback: editorial@rttnews.com