Washington Editor

Sleep easier, insomniacs, because more help is on the way.

The FDA approved a new sleep disorder drug, Lunesta brand eszopiclone, developed by Sepracor Inc. And notably, the agency's OK did not include restrictions on long-term use, an impediment associated with other prescription sleep aids.

"What we wanted, in the long term, was to get the limitation taken off that's on all the other [sleep] drugs, a seven- to 10-day usage limitation," David Southwell, Sepracor's executive vice president and chief financial officer, told BioWorld Today. "Obviously, if you get that taken away, you potentially multiply the prescription size."

That news didn't catch the investment community napping, as shares in the company jumped following the approval. On Thursday, its stock (NASDAQ:SEPR) gained 9.6 percent, or $4.85, to close at $55.30.

Specifically indicated for the treatment of insomnia, which can include difficulty falling asleep as well as difficulty maintaining sleep through the night, Lunesta was approved in three doses: 1-, 2- and 3-mg tablets. The recommended dosing to improve sleep onset and/or maintenance is 2 mg or 3 mg for patients between 18 and 64, and 2 mg for those 65 and older. The 1-mg dose is for sleep onset in older adult patients who primarily complain of difficulty falling asleep.

Southwell noted that the sleep-maintenance aspect of the label distinguishes Lunesta from others in the pack. Its chief competition will be Ambien (zolpidem, Sanofi-Aventis Group), which is indicated for sleep onset only. An extended-release version, designed for sleep maintenance, is under FDA review.

Coinciding with Lunesta's approval news was a sleep-drug consultation call hosted by SG Cowen & Co. in New York. Ian Sanderson, an analyst at the firm who follows Sepracor, said the approval was expected and noted that the product's labeling relative to its lingering effects would prove beneficial in competing with Ambien.

"The language regarding next-day residual effects was superior to that of Ambien," he told BioWorld Today. "Sepracor had been guiding to something more equivalent to that of Ambien."

The product formerly was referred to as Estorra, and an approvable letter received last spring by the Marlborough, Mass.-based company boosted its stock by nearly $16 in one day. It filed for approval early in 2003.

Sepracor based its new drug application largely on data from 24 clinical trials and more than 60 preclinical studies. Six randomized, placebo-controlled Phase III studies for chronic or transient insomnia in both adult and older adult patients served as the basis for the FDA's approval, including notable findings from a six-month safety and efficacy study of Lunesta's use in 788 patients.

"We knew we had a pretty safe drug from the beginning, because it's the single isomer of a drug that's been sold in Europe for 20 years," Southwell said. "And we knew the limitations of existing [sleep drugs]. We were convinced that this drug has a long duration of action, so we really wanted to address the limitations of the rest of the market."

The six-month data revealed statistically significant improvements in patient-reported measures of sleep onset and sleep maintenance compared to placebo for the entire duration of the study, with no evidence of tolerance to the drug, and that long-term study served as a basis for the FDA's decision to not limit its indication to short-term use. The study was the first of its kind for a prescription insomnia agent.

"It came out perfectly and showed that patients who take the drug find that the efficacy is just as good at the end of six months as it is at the beginning," Southwell said. "We were just delighted that the FDA removed the restriction that exists on all other [sleep] drugs."

Sepracor plans to release the product next month, with an internal sales force of about 1,250 ready to promote Lunesta to primary-care doctors, central nervous system specialists such as psychiatrists, and hospitals in the U.S.

The company, which posted the drug's label on its website, pointed to estimates that label 100 million adult Americans as sufferers from either chronic or occasional insomnia, generating a $2.1 billion market in the past year for prescription sleep products. That figure does not include off-label use of central nervous system agents.

"Less than 10 percent of insomniacs seek treatment," Southwell said. "There's sort of a misperception that sleeping pills are addictive and have really bad, next-day effects. The market is truly underserved."

Sepracor expects Lunesta's chief differentiations from its competitors - namely, its potential for long-term use, indication for sleep maintenance and multiple doses - will aid in market penetration.

Southwell said Ambien generated $1.6 billion in sales last year, but another competitor will be Sonata (zaleplon, King Pharmaceuticals Inc.).

"The consultants on our call felt that two things - the maintenance indication and the lack of short-term usage restrictions - have the potential to really transform the market," SG's Sanderson said. "For sleep maintenance, these clinicians primarily use trazadone, an older drug. But they said anywhere from 30 percent to as much as 50 percent of patients fail trazadone, usually within a couple of weeks. [Lunesta] presents a great alternative."

Down the road, an investigational sleep drug called indiplon also could receive approval. A short-acting formulation is under review at the agency, following submission two months ago by San Diego-based Neurocrine Biosciences Inc. It is partnered with New York-based Pfizer Inc., and a long-acting version for sleep maintenance also is part of the program.

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