Sleep, one of the most beautiful experiences in life, is nature's balm for the mind and body. However, not everyone is able to get a good night's sleep. There are various forms of sleep disorders, which affect the quality of sleep. The International Institute of Sleep estimates that more than 70 million Americans suffer from one or more sleep disorders, some of which can be fatal.
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.
Richmond, California-based Transcept Pharmaceuticals Inc. (TSPT) is developing a new drug to help insomnia sufferers return to sleep when they wake up in the middle of the night. The drug candidate known as Intermezzo is at the altar for the second time awaiting FDA decision.
The active ingredient in Intermezzo is zolpidem, the same as that found in well known prescription medication 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 for July 14.
Transcept has a deal in place with privately-held Purdue Pharmaceutical Products L.P that was inked in August 2009 to commercialize Intermezzo. As per the terms of the deal, Purdue is obligated to pay Transcept $6.0 million if Intermezzo is approved on July 14. In addition, Transcept will also receive tiered base royalties on net sales of Intermezzo in the United States ranging from the mid-teens up to the mid-twenty-percent level and $90 million from Purdue upon achieving IP and U.S. net sales targets. Purdue paid a $25.0 million non-refundable license fee to Transcept in August 2009 when the commercialization deal was signed.
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.
Transcept's second product candidate is TO-2061, a low dose form of ondansetron, developed as an add-on therapy in patients with obsessive compulsive disorder who have not adequately responded to approved first-line therapy. According to a study presented in March at the Anxiety Disorders Association of America 30th Annual Conference, 40 percent of patients with obsessive-compulsive disorder receiving first-line treatment with SSRIs (selective serotonin-reuptake inhibitors) or cognitive behavioral therapy require second- or third-line treatments, but remain functionally impaired.
Obsessive compulsive disorder, or OCD for short, is an anxiety disorder characterized by a pattern of repeated obsessions and compulsions. OCD affects approximately 1 to 2 percent of the U.S. adult population and can significantly impair the lives of patients and their families. SSRIs, including Prozac, Luvox, Paxil and Zoloft, and the tricyclic agent, clomipramine, are the only approved medications for OCD.
The phase II trial for TO-2061 was initiated in March of this year. The company plans to enroll 150 patients and the results of the trial are anticipated by mid-2012.
Now, a quick look at the company's balance sheet...
Transcept has no current source of product revenue as it is yet to commercialize a product. The company has incurred net losses since inception. As of March 31, 2011, Transcept had an accumulated deficit of $98.2 million and cash of $63.3 million.
Shares of Transcept have gained more than 35% in the past three months. The stock, which has a 52-week range of $5.84 to $11.88, currently trades around $11.
Updated on July 15
On July 14, the FDA issued a Complete Response Letter for Transcept Pharma's resubmitted New Drug Application for Intermezzo (zolpidem tartrate sublingual tablet).
Though the regulatory agency confirmed that Intermezzo is efficacious for use as needed in the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep, it is concerned how safely the drug can be used based on the information in the Intermezzo NDA.
As a possible path forward, the FDA has suggested that Transcept further investigate whether body weight and demographic factors contribute to differentially elevated blood levels the morning after dosing Intermezzo, develop strategies to decrease next-morning zolpidem levels, and, after mitigation strategies are implemented, demonstrate that next-morning blood levels do not present an unacceptable risk of next-day impairment, which may include the conduct of an additional driving study.
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