No Silver Bullet
Smoking cessation is a market that pharma has largely avoided. Though there are some 1.3 billion smokers worldwide, global
sales of aids for quitting barely hit $1 billion in 2005. Survey after survey shows that seven out of 10 smokers want to stop,
and about half of all daily smokers are actively trying to stop. Yet by many estimates, only one out of 12 quitters remains abstinent after six months, a stat that drops to one
out of 20 at one year and declines from there. The average smoker makes six to nine attempts before getting it right.
Market research told the Chantix team that attitudes toward smoking cessation are rife with cynicism and defeatism. One self-proclaimed
quick fix after another has gone bust, leaving a bad taste for consumers and the media alike. Boasting a novel mechanism of
action, Chantix proved its clear superiority over the competition in clinical trials. Yet Chantix is still no silver bullet—a
fact placed front and center in its branding strategy.
"Smoking is a chronic relapsing condition and an addiction," said Veronique Cardon, group leader of the Chantix US marketing
team. "We wanted to be very careful never to overpromise or position Chantix as a magic pill."
Nicotine-replacement therapies—patches, gums, lozenges, and nasal sprays—deliver a 5 to 10 percent success rate. A course
of psychological or other counseling does about as well. Zyban (bupropion), the first smoking-cessation drug, was introduced
a decade ago and pushed success rates to about 16 percent, according to some studies. In Pfizer trials, the success rate of
Chantix, at one year, reached 22 percent.
"We desperately needed new medications," said Neal Benowitz, an expert in nicotine addiction at the University of California–San
Francisco who advised Pfizer on its clinical trials. "If you were going to pick one first-line drug, this would be it."
Best in brand extension
The Eureka Moment
The man behind Chantix is chemist Jotham Coe. He quit nicotine 20 years ago at age 30, then watched the death of his father
from emphysema and his uncle from lung cancer, both caused by smoking.
Coe joined Pfizer's antismoking project in 1995. He focused on cytisine, a substance derived from plants that has a molecular
structure similar to nicotine's and competes with nicotine for the brain's dopamine receptors. Coe hoped that if he could
tweak the structure of cytisine just right, it could beat nicotine to the punch.
The eureka moment came a year later, after dozens of dead ends. Frustrated, he took a step back and began reviewing earlier
work on morphine-related chemicals (because they are built like cytisine). There he hit upon a paper published in the seventies
that said a morphine molecule seemed to have anti-addictive effects when a nitrogen atom was removed. Sure enough, the same
nitrogen sleight of hand in cytisine neutralized nicotine. By 1997, Coe had a new molecular entity, dubbed varenicline, ready
for clinical trials.
The beauty of varenicline is the double duty it performs as both an agonist and an antagonist of a key nicotine receptor,
says Martina Flammer, MD, senior medical director for Chantix, US and global. "It releases dopamine, but at a much lower level
than nicotine. This takes away the urge to smoke. At the same time, it shields the receptor from nicotine, so that if you
do smoke, you don't get the same pleasure."
Over the next eight years, Pfizer tested varenicline in some 5,000 patients in six clinical trials. Five of the six were classic
placebo trials with smokers who had averaged 21 cigarettes a day for 25 years. The drugmaker was so confident in its product
that it also went head-to-head against Zyban.
Unlike many smoking-cessation studies, Pfizer followed patients for a year, tracking relapses. "We chose the most stringent
endpoint out there," said Flammer.