Success, however, was slow in coming. By 1996, the still-struggling biotech was ready to submit its first drug for approval.
The company had conducted two Phase III trials, one showing significant benefit, the other, mixed results. Despite a clamor
for Myotrophin's approval from patients, advocates, and even Congress, FDA dragged out its decision, finally issuing only
an ambiguous "potentially approvable" letter demanding further studies.
Baldino understandably went ballistic. But somewhat less understandable—for the head of a biotech with no winning track record—was
when he proceeded not only to voice his displeasure with the agency ruling to the press, but to drop the semi-approved drug
for a largely untreatable disease like a spurned suitor.
The drama left Cephalon looking more biowreck than biotech. Its stock tanked, and the New York Times called Baldino "a pariah among investors." "Baldino engaged in a staring contest with FDA," said Tracy. "And he lost." Another
CEO would have been handed his walking papers. But Baldino had an ace up his risk-mitigating sleeve.
The Drug That Never Sleeps
Mention Cephalon to industry insiders, and their instant reply will likely be "Provigil." Cephalon lore has it that Baldino
discovered the brand serendipitously at a small French drug firm called Lafon, where he noticed that lab rats dosed with modafinil—then
being tested, without much success, for depression—were wide awake in daylight "despite being nocturnal creatures," Baldino
It is an anecdote ritually repeated to the press. Another, more ironic, version comes from Arena Pharmaceuticals president
Jack Lief, formerly Cephalon's head of business development. According to Lief, he and a young Cephalon scientist tracked
down the drug, but some company high-ups saw its potential market as too small, since narcolepsy afflicts only about one in
1,000 Americans "At the first executive committee meeting,'" Lief told the Wall Street Journal, "one of the executives said, 'Well, let's just give it back.'"
However it entered Cephalon's sights, the chemical was destined to become not only Cephalon's cash cow but one of the most
pioneering and controversial drugs of the decade. After licensing modafinil in 1993 for $6 million over six years, Baldino
and his team set about building it into a far-flung franchise, with sales expected to top $1 billion by 2010. Still, a so-called
wakefulness-promoting agent—Provigil ("promotes" + "vigilance")—was no slam dunk. Even for those who could grasp Provigil's
promise as a treatment for fatigue related to many kinds of medical conditions, certain doubts and downsides had to be addressed.
Ever since the rise and fall of amphetamines in the '60s, a stigma has been attached to "pep pills." Despite the possible
payday, the proven dangers of addiction and abuse encouraged researchers to shift their focus from how to keep people awake
to how to put them to sleep. But the "if we build it, they will come" confidence demanded by a curious compound in a static
category was Frank Baldino's specialty.
"This is a drug that has no warts on it," he predicted when Provigil won approval from FDA in 1998, three days before its
NDA was to expire. In fact, at every stage of its development, Provigil has lived up to its hype. Unlike Ritalin (methylphenidate),
Dexedrine (dextroamphetamine), and Adderall (mixed amphetamine salts), modafinil is largely free of the side effects and other
complications associated with stimulants. It causes no caffeine jitters, no amphetamine peaks and crashes. Not a single death
has been attributed to it.
"This is the first drug in history to selectively promote wakefulness in a way analogous to how the brain normally wakes up,"
said Dale Edgar, associate professor of psychiatry at Stanford University. In addition to preclinical trials of Provigil for
Cephalon, Edgar has conducted studies financed by the Air Force Office of Research, which now lists Provigil as an official
"go pill" for pilots whose missions stretch out more than 12 hours—on flights, say, to Iraq and Afghanistan.