Cephalon Inc. said it got eye-opening results - in more ways than one - with its approved sleep disorder drug, Provigil, when it showed statistical significance in both primary endpoints of a 12-week Phase III study in 209 patients who have the condition when related to shift work.
"This study was the last we had anticipated completing" before the West Chester, Pa.-based company files a supplemental biologics license application that is expected by the end of the year, said Sheryl Williams, director of product development for Cephalon.
Subjects in the study were given either 200 mg of Provigil (modafinil) or placebo as a single dose before the start of their night shift. Provigil significantly improved wakefulness compared to placebo (p<0.01), as measured by the Multiple Sleep Latency Test. Patients also showed significant improvement in their clinical condition as measured by the Clinical Global Impression of Change when compared to patients treated with placebo (p<0.0001).
Shift-work sleep disorder consists of insomnia or excessive sleepiness in relation to work scheduled during what would be considered the usual hours of sleep, and typically arises during night shifts, causing those afflicted to fall asleep or suffer impaired mental ability as a result of reduced alertness.
In the study, Cephalon found that patients with shift-work sleep disorder had levels of pathological sleepiness at baseline that were similar to patients with untreated narcolepsy or untreated obstructive sleep apnea.
"Narcolepsy is the most serious model of sleepiness, and there was a perception that shift-work sleep disorder would be some milder form," Williams told BioWorld Today, but added "how surprised even the experts were that these people were as pathologically sleepy as they were."
Until recently, many called the shift-work problem "essentially a lifestyle issue," she said. "That may have been true before society was essentially 24/7,'" Williams said, but no longer.
About the use of Provigil off-label for shift-work disorder, she said, "we don't have any data on whether it's being used for that purpose, and we haven't heard anything from investigators in the study."
In September, Cephalon reported results from a study in 248 children between the ages of 6 and 13 showing that Provigil significantly improved symptoms of attention deficit hyperactivity disorder.
"We're exploring our strategy and evaluating the opportunity" with regard to Provigil in that indication, Williams said.
The drug, whose exact mode of action is unknown, was approved in December 1998 for excessive daytime sleepiness associated with narcolepsy and launched in February of the next year. (See BioWorld Today, Dec. 21, 1998.)
William Tanner, analyst with Leerink Swann & Co. in Boston, estimated sales of Provigil would reach about $207 million by the end of 2002. Behind it are Cephalon's Actiq (fentanyl) for breakthrough cancer pain episodes, which is expected to sell about $106 million, and Gabitril (tiagabine hydrochloride), marketed under an agreement with Abbott Laboratories Inc., of Abbott Park, Ill., for the adjunctive treatment of partial seizures associated with epilepsy. Gabitril is expected to sell about $44 million this year, Tanner said in a research report.
Cephalon's stock (NASDAQ:CEPH) moved up $2.29 Wednesday to close at $48.82.