Big drug companies, cold turkey and what we don't know about America's No. 1 new anti-smoking drug

Last week started on a high note for Chantix, Pfizer Inc.'s hot-selling smoking-cessation drug.

With more than 3 million Americans on its prescription rolls, the largest share of the $1 billion smoking-cessation market and a new TV commercial in heavy national rotation, Chantix got a nice boost Monday when a respected medical newsletter published this assessment: Varenicline, the drug marketed by Pfizer as Chantix, 'is the most effective drug available' for smoking cessation.

Then Tuesday rolled around.

The U.S. Food and Drug Administration announcement came quietly in an afternoon e-mail update: The agency that had fast-tracked its review of varenicline in 2006 was now asking Pfizer to provide more data about the drug's possible mental health side effects: depression, outbursts of rage, suicidal thoughts. The FDA collected about 100 disturbing patient reports, headlined by the high-profile September shooting death of a Dallas musician, before making its decision.

Pfizer responded with a statement pointing out that there was no scientific evidence of a causal link between its product and the alarming reports. But Chantix's run of unbroken good news had come to an end, and John R. Polito of Mount Pleasant was anything but surprised.

Polito, a retired Navy sailor, is an anti-smoking activist and cold-turkey advocate at the Web site www.whyquit.com. He's been updating a detailed online critique of Pfizer's Chantix research since the drug went on the market in August 2006.

That critique covers everything from the conduct of the trials to the drugmaker's claims about effectiveness, but on Tuesday, the FDA's announcement emphasized Polito's biggest complaint: 'We need more data,' he said.

More data seems a prudent, sensible caution, echoing the concerns of the consumer-advocacy group Public Citizen, which put Chantix on its 2007 Worst Pills list and advises people to steer clear of varenicline for another seven years.

But there's another side to this, and here's how it begins: 400,000 American deaths per year are attributable to cigarette smoking, with an annual direct health care cost estimated at $1.09 billion. And quitting is difficult, with statistics suggesting that 93 percent of unaided, go-it-alone attempts end in failure within the first year.

Which makes Chantix's claim to a 22 percent 12-month success rate in its clinical trials reason enough for physicians such as Dr. Bob Mallin of the Medical University of South Carolina's department of family medicine to sit up and take notice.

'Everything we do in medicine is a cost-benefit analysis,' Mallin said. 'Considering the benefits (of quitting) to the patient, the cost would have to be something pretty bad to cancel it out.'

Mallin, who is certified in the treatment of addictions, leads smoking-cessation groups and figures he's prescribed Chantix to about 100 patients.

'I'm not somebody who usually gets excited about new drugs because they're usually disappointing,' he said.

But he suspects that the success rates for his Chantix patients will exceed 40 percent. He calls the drug 'a different ball game.'

Here's why: Before varenicline, smokers in search of chemical assistance had two options: Zyban, an anti-depressant that seemed to cut down on smokers' cravings, and nicotine-replacement therapy (NRT), typically delivered via gums, inhalers and skin patches.

The problem? Anti-depressants and NRT prescribed in combination with 'psycho-social support' produce success rates that are only marginally better than participation in support groups alone, while creating secondary dependence issues and costing consumers and insurance companies millions of dollars. Chantix shows potential for improving those odds by attacking the problem differently.

Cigarette smoking is the most effective way of delivering nicotine, the world's most addictive substance, to the bloodstream. Once the drug reaches the brain, its molecules bind to receptor cells, kicking off a chemical cascade that gives the smoker a burst of feel-good pleasure.

But with varenicline filling the brain's nicotine receptor sites, a smoker is denied that chemical rush. The drug provides quitters with an elevated level of dopamine while reducing cravings and physical withdrawal symptoms.

Dr. Wayne Weart of MUSC's College of Pharmacy calls it 'the most effective agent we've ever had' for combating nicotine addiction, and apparently doctors around the country have agreed. Pfizer says more than 3 million Americans have been prescribed Chantix since August 2006, and industry analysts predict peak annual sales of $1.3 billion.

Which is where Polito speaks up. He says those statistics that cite 93 percent failure rates for cold-turkey quitters mask a larger truth: While

individual

quitting attempts succeed only 7 percent of the time, the vast majority of former smokers quit

without

chemical assistance. If pharmacology alone fails without peer support and improves on support-group success rates only marginally, then why is the government so intent on promoting expensive, drug-based therapies?

Those clinical trial success rates? He contends they're artificially inflated.

Side effects? Polito suspects that the drug's 'rare' side effects will prove to be far more common outside the clinical trials. Reason? Smokers with major medical conditions, including substance abuse problems or mental illness, were excluded from the clinical trials.

'This messes with chemical pathways in the brain,' he said. 'How do (drugs and alcohol) interact with it? Unless you've studied it, you don't know, and we haven't studied it.'

'Why not?' is the big question for Dr. Sidney Wolfe, director of health research for Public Citizen. His answer: the Prescription Drug User Fee Act, a 1992 law that allows the FDA to bill pharmaceutical companies for the cost of approving their products. The FDA estimates its 2007 collections under the act will exceed $259 million and cover the majority of its drug-approval expenses.

That's caused a cultural shift at the agency, Wolfe said, with quicker turnaround times and a more accommodating attitude toward drugmakers. 'The (pharmaceutical) industry is viewed by some people in the FDA as 'our client. 'They're paying our salaries.' Twenty years ago, if a drug went through clinical trials and there were more serious questions, the attitude was, 'Let's do more studies.' Not anymore.'

The FDA disputes that charge, though Celia Winchell, the leader of its medical team for addiction drug products, said Wednesday that when it comes to debate over how much data is enough, 'there certainly is tension in that area.'

Winchell said it's too early to predict whether the agency will require new trials, but whatever the outcome of the FDA's Chantix study, more new anti-smoking drugs are lining up in the approval pipeline, including two proposed drug therapies and three vaccines designed to prevent nicotine from entering the brain. Stay tuned.

Reach Dan Conover at conover@postandcourier.com.