Nicotine addiction is one of the most prevalent addictive behaviors worldwide. According to the World Health Organization, 1.3 billion men, women and children worldwide are smokers. In spite of increased awareness and action on the part of both governments and individuals, tobacco continues to be the leading cause of preventable disease and death in the U.S., as well as many other countries. According to WHO, there are nearly 5 million tobacco-related deaths worldwide each year and nearly half of the smokers in the world today will die as a cause of their addiction.

Although the development of pharmacotherapies for nicotine addiction has traditionally centered on nicotine replacement, more recent discoveries have led to a new line of research into non-nicotine therapies, including the antidepressant bupropion.

Nicotine works upstream of dopamine to reinforce smoking behavior by activating nicotinic acetylcholine (AChE) receptors located in dopamine reward centers in the midbrain. Nicotine receptor modulation has thus been identified as a mechanism for treating nicotine addiction.

New data reported late last year show that Pfizer's varenicline tartrate, a neuronal nicotinic alpha4beta 2 receptor partial agonist, is a more effective antismoking agent than bupropion. In two double-blind, placebo-controlled studies involving about 2,000 smokers, patients received either varenicline (1 mg b.i.d.), bupropion (150 mg b.i.d.), or placebo for 12 weeks. Patients were followed for an additional 40 weeks without treatment. In both studies, 44% of varenicline-treated patients quit by the end of the 12-week treatment period, significantly more than the 30% of bupropion-treated patients who quit. Among patients who received placebo, 18% had quit by the end of the 12-week treatment period. The odds of quitting smoking for patients taking varenicline were approximately two times higher than 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. A third study randomized smokers who successfully quit smoking after 12 weeks of varenicline to 12 weeks of either placebo or an additional 12 weeks of varenicline. These patients were followed for 28 weeks after the treatment period. A total of 71% of patients who received the additional course of varenicline remained abstinent after six months, compared to 50% who received placebo as the second course.

Pfizer has submitted regulatory submissions in the U.S. and Europe seeking approval of varenicline for smoking cessation; in the U.S., the FDA has granted priority review status to the product. Upon approval, Pfizer intends to market varenicline under the brand name Champix®.