It seemed like the offer of a lifetime: earn $2,500 (Rs1.15 lakh) by flying to France aboard a private luxury jet.
But as the fine print made clear, there’d be no Eiffel Tower or chateaux, no foie gras or Bordeaux. Travellers were confined to a laboratory in either Toulouse or Rouffach with electrodes attached to their heads, testing whether a drug could keep their jet-lagged bodies awake.
That drug, Nuvigil from Cephalon Inc., could become the first medicine specifically approved by the US Food and Drug Administration (FDA) to combat jet lag.
A jet lag antidote might seem to be the latest lifestyle drug, a further step in the “medicalization” of something that is not an illness. But sleep specialists, who call the affliction “jet lag disorder”, say that while not exactly a disease, it is a condition that can be dangerous—as when someone tries to drive a car right after arriving in a distant time zone.
For Cephalon, a drug company in Frazer, Pennsylvania, with a reputation for aggressive business tactics, the approval for jet lag is part of a plan to extend the patent protection for its core franchise in stay-awake drugs.
Nuvigil is a slight modification of Provigil, an older stimulant that will face generic competition in 2012. Provigil sales were around $1 billion in 2008, accounting for half of Cephalon’s revenue. Nuvigil, which first went on sale in June and has a longer patent life, had sales of $38 million through September.
Jet lag results when the body’s internal clock is out of sync with daily life, making people sleepy when they want to be awake and wakeful when they want to sleep. It is one of several so-called circadian rhythm disorders that are attracting increasing attention from the pharmaceutical industry. Some studies suggest that disruption of the daily rhythms can contribute to obesity, mental illness and other ailments.
Nuvigil and its predecessor, Provigil, are already approved to treat the excessive sleepiness associated with narcolepsy, sleep apnea and “shift work sleep disorder”—which can affect people who work the graveyard shift. But the drugs are prescribed widely to treat the sleepiness associated with other diseases, or even just to help healthy people get by on less sleep. For jet lag, Nuvigil would be approved to treat only the sleepiness associated with jet lag disorder—not to shift the body’s clock to the new time zone.
“It’s something that can help you overcome the symptoms, but not the cause of the problem,” said Charmane I. Eastman, director of the biological rhythms research laboratory at Rush University Medical Center in Chicago, who was not involved in Cephalon’s trial.
Cephalon plans to aim Nuvigil at business travellers who might go to Europe for a couple of days, not those staying longer term. For a short trip, “you don’t want to shift your circadian clock very much”, said Lesley Russell, Cephalon’s chief medical officer.
The company’s executives are not predicting how much an approval for jet lag would add to Nuvigil sales. The drug would be taken for only a day or two to treat jet lag, whereas other uses involve taking it for long periods.
A market challenge for the firm will be that Nuvigil costs at least $9 a pill, with one pill usually taken each day. Nuvigil will have to compete with inexpensive jet-lag treatments such as coffee, sleeping pills and the nutritional supplement melatonin.
Nuvigil has not been clinically compared with those remedies, some of which might work as well but have never been specifically approved for jet lag. Sleeping pills, for example, are approved to treat insomnia, whatever the cause, so there has been no need to seek a specific approval for jet lag, said Thomas Roth, director of the sleep disorders and research centre at Henry Ford Hospital in Detroit and a consultant to Cephalon.
And stimulants such as caffeine and amphetamines, he said, are generic, so manufacturers have no incentive to conduct clinical trials.
But even if Nuvigil sales for jet lag are small, FDA approval would help Cephalon advance its franchise-extending strategy.
But Provigil will face generic competition in April 2012 under terms of an agreement Cephalon made with several generic drug manufacturers. The US Federal Trade Commission has sued Cephalon, saying it paid off those generic manufacturers to delay the advent of competition.
Cephalon, which denies the charges, is trying to shift patients from Provigil, also known as modafinil, to the similar but slightly longer acting Nuvigil, or armodafinil. Nuvigil has patent protection until 2024, though generic drug firms are already moving to challenge those patents.
To get patients to shift, Cephalon has raised the wholesale price of Provigil to $13.60, from around $5.50 a pill five years ago, including a 29% increase in November. So Provigil is now 50% more expensive than Nuvigil.
And Cephalon is also trying to have Nuvigil approved for new uses beyond those of Provigil.
Not only would jet lag be the first of these new uses, but its formal approval for that condition would enable Cephalon to promote Nuvigil to a broad array of doctors, not just those who treat sleep disorders.
“What a jet lag indication allows you to do is go to virtually every doctor, because every physician will at some point treat a patient who will have jet lag,” said Corey Davis, an analyst at Jefferies and Co.
©2010/ THE NEW YORK TIMES