By Jim Shrine

Cephalon Inc. won its first product approval with the FDA's clearance of Provigil (modafinil) to treat excessive daytime sleepiness associated with narcolepsy.

The product, which still needs final scheduling from the Drug Enforcement Agency, is expected to be on the market in mid-February. The approval came exactly two years after filing of the new drug application (NDA), and represents the first novel treatment for the neurological disease in 40 years.

"It's a new beginning for us," Frank Baldino, Cephalon's president and CEO, told BioWorld Today. "Cephalon has had a tough couple of years. We worked hard to get this drug approved. With it, we think we can be profitable in 2001. Most of our activities going forward will be focused on expanding the use of the product."

Cephalon's stock (NASDAQ:CEPH) gained $1 per share Monday, or 12.2 percent, to close at $9.187. The company's shares traded as high as $10.375.

West Chester, Pa.-based Cephalon already has a U.S. sales force of 45 in place. And it already has experience selling the drug, through an earlier product approval in the U.K.

David Stone, managing director in the Boston office of SG Cowen Securities Corp., said the approval is "a good piece of news for a company that has had a pretty long trek with the FDA. Perhaps because of that, it's being regarded by the market as pretty positive news, even though it happened as expected. What Provigil can do for Cephalon is take the company to profitability over a couple of years with sales of this product, along with co-promotion payments it gets from other pharmaceutical companies."

Sales Projected To Hit $90M In 2001

Stone projected Provigil sales of $12 million to $13 million in 1999; $50 million in 2000; and $90 million in 2001. "There is a considerable potential for off-label use and expanded indications beyond narcolepsy," Stone said.

The synthetic compound was licensed in 1993 from Paris-based Laboratorie L. Lafon, which has been selling the drug in France since 1994. Cephalon has been selling it in the U.K. since March, and believes approvals in Ireland and Austria are "imminent," while approvals are being pursued in Switzerland and Italy, where Cephalon also has rights.

Stone said current therapies for adults with narcolepsy and children with attention deficit disorder involve amphetamine-like products. Provigil has advantages over them, he said, in that it's not addictive and doesn't produce the cardiac-related side effects. It also comes without the highs and lows associated with amphetamines.

"Doctors we've talked to are excited about prescribing Provigil," he said.

Cephalon filed its Provigil NDA in December 1996 and a year later got an approvable letter that asked for more information, which it took Cephalon six months to provide. The approval then came six months later.

The approved dosing is 200 milligrams per day, in tablet form. That was one of two doses used in two pivotal studies that showed the drug improved patient wakefulness and well-being. An estimated 125,000 people in the U.S suffer from narcolepsy, a chronic, lifelong disorder that causes people to fluctuate between sleeping and waking.

Scott Melville, Cephalon's senior director of corporate and public affairs, said narcolepsy often is misdiagnosed and under-diagnosed. On average, people with the condition go through 10 to 15 years of symptoms and five doctors before they are properly diagnosed, he said. "We're hoping to raise awareness of the signs and symptoms of narcolepsy, so people will see their doctors sooner," Melville said.

Baldino said the drug, by inhibiting GABA neurotransmitters, acts selectively on the parts of the brain involved in sleep and wakefulness - unlike stimulants, which work on all centers of the brain.

In the next year, he said, results will be available from trials assessing Provigil's effect on daytime sleepiness from other disorders. One of those, sleep-induced apnea, affects 12 million people. Other areas in which the drug might be useful, he said, are Parkinson's disease and multiple sclerosis.

Stone said Alzheimer's disease is another potential target. *