By Randall Osborne

Almost a year to the day after submitting a new drug application (NDA) for its narcolepsy treatment to the FDA, Cephalon Inc. received a letter from the agency saying it would approve Provigil (modafinil) when product labeling and other issues are settled.

Provigil, a synthetic compound licensed in 1993 by West Chester, Pa.-based Cephalon from Laboratoire L. Lafon, of Paris, targets the sleep disorders narcolepsy and idiopathic hypersomnia, apparently by affecting alpha adrenergic receptors in the brain.

"The precise mechanism of action is not well understood yet, but we know it's an effective agent in promoting wakefulness and reducing the number of sleep attacks," said Jason Rubin, vice president of corporate communications for Cephalon.

Cephalon filed the new drug application FDA for Provigil Dec. 30, 1996. It was the company's first such filing. (See BioWorld Today, Jan. 2, 1997, p. 1.)

Provigil already has been approved in the U.K., where Cephalon holds the marketing rights. In France, Laboratoire L. Lafon markets the drug. Cephalon also has marketing rights in Japan and Mexico, as well as Ireland, where it is under review.

Among the issues to be resolved, Rubin said, is drug scheduling: the classifying of Provigil according to a system under the management of the federal Drug Enforcement Administration, which regulates how such treatments are manufactured and dispensed.

"We're prepared to move ahead with the FDA as quickly as possible, but I couldn't speculate about what the timing [of approval] might be," Rubin said.

Narcolepsy is a condition that causes those afflicted to waver constantly between waking and sleeping. The disease typically is treated with amphetamines or similar drugs, which may cause mood swings and lead to addiction. Phase III trials of Provigil showed the drug effective, improving patients' wakefulness and overall well-being without the negative side effects. (See BioWorld Today, March 15, 1996, p. 1.)

Rubin said he could not speculate on the size of the market for Provigil. "We know there are estimated to be 125,000 people with narcolepsy in the U.S., and some subset of those is being treated today," he said.

Still Waiting For FDA Action On Myotrophin

Almost a year has passed since the NDA was submitted for Cephalon's other lead product, Myotrophin (recombinant human insulin-like growth factor-1), and the FDA has not decided whether to grant the go-ahead for marketing. Myotrophin is Cephalon's proprietary drug and is being developed in a partnership with Chiron Corp., of Emeryville, Calif.

In January 1994, Chiron agreed to buy 750,000 shares of Cephalon's common stock and warrants to purchase an equal number of shares for $15 million. As part of that agreement, Chiron would manufacture Myotrophin and Cephalon would market it to neurologists in the U.S., with the companies likely to collaborate on European sales.

Myotrophin is a treatment for amyotrophic lateral sclerosis, which also is called Lou Gehrig's disease, a fatal illness characterized by chronic, progressive deterioration of motor neurons. In August, an FDA advisory panel voted against approval, citing conflicting clinical results between trials in North America and Europe. Cephalon declined to conduct another trial, which the FDA said would be the best way to resolve the discrepancies. The company submitted more data to the agency instead. (See BioWorld Today, Aug. 12, 1997, p. 1.)

"It's still under review," Rubin said. "The FDA has until May [1998] to decide on Myotrophin." The NDA was resubmitted in November.

Also in November, TAP Holdings Inc., of Deerfield, Ill., extended for another year its funding of Cephalon's research into tyrosine kinase inhibitors. The TAP deal, which began in 1994 and netted Cephalon about $7 million this year, has Phase I trials under way for CEP-2563, a small molecule shown to prevent the growth of cancer cells. The collaboration expanded in 1996 to include more drug candidates, and all cancers. (See BioWorld Today, Nov. 26, 1997, p. 1.)

Cephalon's stock (NASDAQ:CEPH) closed Tuesday at $12.187, up $1.75. *