Source: New York Times
September 26, 2003

More Uses for Stimulant Endorsed

By ANDREW POLLACK with ALICIA AULT

An advisory panel to the Food and Drug Administration endorsed yesterday new uses for a stimulant that keeps people awake with fewer side effects than caffeine or amphetamines.

The panel said the drug, Provigil, now approved only for narcolepsy, could also be used to fight sleepiness in workers who cannot adjust to night shift jobs and in people who do not sleep well because of a breathing disorder known as obstructive sleep apnea.

But with some members expressing concern that the drug might be overprescribed, the committee did not endorse the request by the drug's manufacturer, Cephalon, that it be approved for all sleep disorders. The panel, which met in Bethesda, Md., split 4 to 4 on that question.

The F.D.A., which usually follows the recommendations of its advisory panel, is expected to make at least a preliminary decision by Oct. 20 on whether to expand the approved uses of Provigil.

Doctors say that Provigil, known generically as modafinil, can keep people awake with less of the jitteriness and risk of addiction of caffeine or amphetamines. It was approved in 1998 to treat sleepiness from narcolepsy, a rare disease in which people uncontrollably fall asleep.

But most prescriptions have been written for other uses, like the sleepiness or fatigue associated with depression or multiple sclerosis. There has been concern in the medical community that Provigil could become a lifestyle drug, used as a substitute for sleep by those who want to work or play longer.

Cephalon, a small pharmaceutical company in West Chester, Pa., said the new uses, if approved by the F.D.A., would permit its sales people to call upon general practitioners in addition to the sleep specialists, psychiatrists and neurologists they now visit. That could increase sales of Provigil, its biggest product. Sales last year were $196.3 million. but the once torrid rate of growth has been moderating.

Frank Baldino Jr., chief executive of Cephalon, said the company was "pretty excited" by the panel's vote and planned to expand its sales force to 450 people by early next year from 330 now so it could begin calling on general practitioners. He said that even if the F.D.A. expanded approval of the drug only for sleep apnea and shift work, rather than for all sleep disorders, the company would benefit. "As long as we can legitimately call on G.P.'s and access the population they treat, the sales of the drug will be larger," he said on a conference call.

Analysts differed. Jim Birchenough of Lehman Brothers said yesterday in a note to clients that "we do not see upside over all" from the panel's vote. If the drug is approved only for the two specific conditions, general practitioners will probably refer patients to the sleep specialists already visited by Cephalon's sales representatives, he said.

But Kris Jenner, portfolio manager of the T. Rowe Price Health Sciences Fund, which owns Cephalon shares, said the panel vote left room for a broader label. "I think that Cephalon is in the process of developing an entirely new therapeutic class, which is wakefulness," he said.

Cephalon shares, which did not trade until the panel meeting ended, rose $1.23, to $46.90.

Cephalon hoped to get approval for sleepiness caused by all sleep disorders by showing that the drug worked in three representative conditions narcolepsy, shift work sleep disorder and sleep apnea, a condition in which people awaken briefly many times a night because their breathing stops. The F.D.A. has approved drugs to treat pain without requiring clinical trials for all causes of pain.

But the panel was reluctant to go beyond the conditions tested in clinical trials. One concern was that doctors, particularly general practitioners, might find it too convenient to prescribe Provigil to treat sleepiness, which is a symptom, rather than treating the underlying disease, or even checking to see if there is an underlying disease.

"We're talking about treating a symptom without understanding the many possibilities that lead to that symptom," said Claudia Kawas, the panel's chairwoman and a neurologist at the University of California, Irvine.

Another concern was that the drug would be prescribed for nonmedical conditions, for someone who does not get enough sleep, for example, or someone with temporary jet lag.

Cephalon said it had not seen much evidence of such use. It said Provigil should not be used to fight sleepiness in just any night shift worker, only those with a clinical condition called shift work sleep disorder. People with that condition never quite adjust to night work.

But Lois E. Krahn, a panel consultant and chairwoman of psychiatry and psychology at the Mayo Clinic in Scottsdale, Ariz., said, "How possible will it be for the ordinary clinician to make that distinction?"

F.D.A. officials suggested during the meeting that they were not overly concerned with use of the drug by healthy people because the drug was generally safe. Robert Temple, an F.D.A. official, said it was "not completely obvious" that use of the drug just to keep healthy people alert would be a bad thing, because sleepy people could endanger others.

"If they're driving next to me, I think I'd prefer they be on it," he said.




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