Varenicline is a selective nicotinic acetylcholine receptor partial agonist, the first in a new class of potential smoking-cessation therapies. This month, Pfizer submitted a New Drug Application to the Food and Drug Administration (FDA) and applied for European registration for varenicline for smoking cessation. Upon approval, Pfizer Inc. intends to market varenicline under the brand name Champix.

Encouraging Results

Participants in two double-blind placebo-controlled studies -- about 2,000 smokers, in all -- received either varenicline (1 mg twice daily), bupropion, marketed as Zyban (150 mg twice daily), or placebo for 12 weeks. They were followed for an additional 40 weeks without treatment.

In both studies, 44 percent of varenicline-treated patients quit by the end of the 12-week treatment period, significantly more than the 30 percent of patients who quit after taking Zyban.

Eighteen percent of those who received a placebo had quit by the end of the 12-week treatment period. The odds of quitting smoking for patients taking varenicline were approximately twice as good as those on bupropion, and four times higher than those on placebo.

After one year, patients who received varenicline were significantly more likely to remain smoke-free compared to patients who received bupropion or placebo.

"These results are very encouraging," says Dr. Serena Tonstad, head physician, Department of Preventive Cardiology, Ulleval University Hospital, Norway.

"Smoking doubles a person's risk of cardiovascular disease and triples the risk of death from heart attack," Dr. Tonstad notes. "Patients who are serious about quitting should seek medical support and treatment to help them ultimately succeed."

A third study of smokers who successfully quit smoking after 12 weeks of varenicline randomly placed participants in groups that received 12 weeks of either placebo or an additional 12 weeks of varenicline. These patients were followed for 28 weeks following treatment.

There were significant benefits observed among patients who received additional treatment after successfully quitting on varenicline. Seventy-one percent of them remained smoke-free after six months, compared to 50 percent who received placebo.

Relieves Craving and Withdrawal Symptoms

Smoking is the leading preventable cause of illness and premature death in the United States. Each year, smoking is responsible for 140,000 deaths from cardiovascular disease by increasing the risk of heart attack, stroke and sudden death. Annual health-related costs in the United States are estimated to be $167 billion.

Smoking is a chronic relapsing condition that involves a physical and psychological addiction to nicotine. When a smoker inhales a cigarette, nicotine reaches the brain in less than 10 seconds. The nicotine binds to receptors, leading to the release of dopamine in the pleasure centers of the brain.

As nicotine levels drop, satisfaction recedes quickly, resulting in craving and withdrawal symptoms, such as irritability and anxiety. This, in turn, leads to continued smoking behavior.

"Varenicline was specifically designed to work at the same receptor site as nicotine to relieve craving and withdrawal symptoms while at the same time blocking the reinforcing effects of nicotine," says Dr. Salomon Azoulay, varenicline development lead at Pfizer.

In all trials, varenicline was well tolerated, with overall discontinuation rates similar to placebo. The most common side effects included nausea, headache, trouble sleeping and abnormal dreams.