West Coast Editor

News, as expected, that the FDA regards Cephalon Inc.'s Nuvigil for sleepiness as approvable came with the proviso of bold-face label warnings, as overhang remained from a probe into marketing practices related to the firm's pain drugs, and investors stayed wary about maneuvers to counter generic threats.

Shares of Frazer, Pa.-based Cephalon (NASDAQ:CEPH) closed Monday at $75.96, up $4.75, or 6.7 percent.

Nuvigil (armodafinil), a single-isomer formulation of modafinil, is designed to improve wakefulness in particularly difficult patients suffering from excessive sleepiness associated with narcolepsy, shift-work sleep disorder and obstructive sleep apnea/hypopnea syndrome.

Cephalon submitted its new drug application to the FDA in March 2005, and the first approvable letter came about a year ago. Included in the drafted label proposed by the latest letter is a warning section about skin rash and hypersensitivity in patients taking Nuvigil. A similar warning would be added to the label for Provigil (modafinil), Cephalon's approved narcolepsy drug.

The FDA demands no new trials, but wants a standard safety update on Nuvigil from trials conducted since the last update in June, and wants to see introductory promotional materials. Cephalon will submit its response within 30 days, and the agency is expected to finish reviewing Nuvigil within 60 days thereafter.

In August, Cephalon dumped a different formulation of modafinil intended for attention-deficit/hyperactivity disorder, after getting a not-approvable letter from the FDA because of a single suspected case of a rare but serious skin rash called Stevens-Johnson syndrome. (See BioWorld Today, Aug. 11, 2006.)

That letter followed a vote against Sparlon by the Psychopharmacologic Drugs Advisory Committee, which voted unanimously that the drug is effective for its intended use but also recommended that the company collect additional data to support its safety in children and adolescents.

"I wouldn't say [the label proposal for Nuvigil and Provigil] was a surprise," said Jenifer Antonacci, spokeswoman for Cephalon.

The FDA's decision favoring approval lets Cephalon look ahead to shifting Provigil patients to Nuvigil in 2009, ahead of the launch in 2012 of a handful of generic versions of Provigil.

Cephalon's way of handling trouble with generics - by striking deals with the drugmakers - has not been without snags. Last June, Apotex Corp., of Toronto, filed a lawsuit against the firm and licensees Barr Laboratories Inc., Mylan Laboratories Inc., Teva Pharmaceutical Industries Ltd. and Ranbaxy Laboratories Ltd., accusing them of trying to create a monopoly. Cephalon's agreements with the companies keep them from selling generic Provigil before spring 2012, and the case brought scrutiny by the Federal Trade Commission.

The company has met new problems this year. Last month, Rep. Henry Waxman (D-Calif.), chairman of the House Committee on Oversight and Government Reform (which oversees pharmaceutical marketing practices) made public an inquiry into marketing practices of Cephalon, along with two other pharmaceutical companies and a pair of medical device firms.

"There haven't been any hearings yet," Antonacci said. "We did get a letter requesting information, and we're complying."

The probe is related to the marketing of Cephalon's breakthrough cancer pain narcotics, Actiq and Fentora - often prescribed off-label - and follows by less than a month a warning letter from the FDA about Provigil. The letter cites promotional material that creates new "intended uses" for the compound "for which the product lacks adequate directions, broadens the indication for Provigil and fails to communicate any risks associated with its use."

Antonacci said the material in question was used only once.

"We've gone back, per the FDA's request, and looked through our marketing materials and made sure there was nothing similar to this," she told BioWorld Today, adding that other material is "well within the guidelines" set by the agency.