West Coast Editor
Cephalon Inc. filed a new drug application for Nuvigil, the second generation of its approved Provigil (modafinil) therapy for excessive daytime sleepiness, shift-work sleep disorder and obstructive sleep apnea.
Nuvigil (armodafinil), a single-isomer version of Provigil's active ingredient, targets the same disorders, but stays active longer.
"The package that we submitted to the FDA includes the clinical data on studies looking at that issue," said Sheryl Williams, spokeswoman for Frazer, Pa.-based Cephalon.
The firm's stock (NASDAQ:CEPH) closed Friday at $46.02, down 81 cents.
In four 12-week studies, daily doses of 150 mg and 250 mg of Nuvigil or placebo were given to about 1,000 patients. Primary endpoints in all studies were measures of objective sleep latency (by way of the Maintenance of Wakefulness Test or Multiple Sleep Latency Test) and the physician rating of Clinical Global Impression-Change.
Each study found that patients treated with the drug showed a statistically significant improvement on both primary endpoints compared to placebo, with all "p" values less than 0.05. Recordings and patient diaries showed that, compared with placebo, Nuvigil did not disturb patients' normal sleep schedule.
Full data will be presented for the first time at a scientific meeting in June, Williams said. Provigil was approved in 1998.
Cephalon also markets Gabitril (tiagabine hydrochloride) for epileptic seizures and Actiq (oral transmucosal fentanyl citrate) for cancer pain. The firm reported $1 billion in revenues for 2004, up 42 percent at the previous year, and at the end of March got an approvable letter from the FDA to sell a sugar-free formulation of Actiq.
Also pending is a supplemental new drug application seeking approval of a once-daily dose of modafinil called Attenace for attention deficit/hyperactivity disorder in children and adolescents between the ages of 6 and 17, with a launch expected by early 2006.
Another narcolepsy drug recently making news - with Cephalon's Provigil - is Xyrem (sodium oxybate) from Orphan Medical Inc., of Minneapolis. The FDA accepted for filing the supplemental NDA for Xyrem, which is approved for cataplexy, or sudden loss of muscle tone, in narcolepsy patients. Orphan Medical wants to market the drug with a label that includes reduction of excessive daytime sleepiness and the improvement in fragmented nighttime sleep. (See BioWorld Today, Jan. 19, 2005.)
One of two Phase III studies with Xyrem, called Exceeds, evaluated the drug when used alone or with Provigil, and showed that the combined use of the drugs gained a greater response than either agent alone.
A number of patients are on both drugs already, Williams pointed out.
Xyrem is the first and only approved treatment for cataplexy, and no treatments cover all of the primary symptoms of narcolepsy. Before Xyrem, doctors gave antidepressants to treat cataplexy, stimulant medications for excessive daytime sleepiness, and sedative-hypnotic drugs for disrupted nighttime sleep.
Tim McGrath, vice president and chief financial officer for Orphan Medical, noted the trial testing Xyrem with Provigil was a four-arm, blinded study.
"We were trying to answer a question along the lines of, Can Xyrem treat [daytime sleepiness] similar to a stimulant?'" McGrath told BioWorld Today, and Provigil, as the most prescribed stimulant, was the logical choice.
As for Provigil's owner Cephalon, the firm has two compounds in Phase III trials, including the approved seizure drug Gabitril, which is being tested against generalized anxiety disorder. An NDA could be submitted early next year. Oravescent fentanyl for breakthrough cancer pain - acquired through the $515 million buyout of CIMA Labs Inc., of Eden Prairie, Minn., completed last year - is up for possible approval in late 2006. (See BioWorld Today, Nov. 5, 2003.)