FDA approves varenicline for smoking cessation

OB/GYN News, June 1, 2006 by Timothy F. Kirn

The newly approved drug varenicline may help a significantly higher percentage of patients quit smoking than bupropion, according to Food and Drug Administration officials and others.

The drug was judged from early trials to show such promise that it was put on the approval fast track 6 months ago.

"This is the first time we have had a drug that we can say is better than the other drugs," said Dr. John R. Hughes, a professor of psychiatry at the University of Vermont, Burlington, and a founding member of and spokesperson for the Society for Research on Tobacco and Nicotine. "I think this is a significant advance."

Varenicline tartrate (Chantix, Pfizer Inc.) is approved for use twice a day (1 mg) for 12 weeks, with another 12 weeks for those who are successful in quitting during the first 12 weeks. The drug is not approved for adolescents. In the trials, varenicline was never used in combination with other smoking-cessation agents, so the label will recommend not combining the drug with bupropion or a nicotine patch.

The FDA had six trials of varenicline to review for approval, five of which were placebo-controlled and randomized, said Dr. Curt Rosebraugh, a deputy director of the Center for Drug Evaluation and Research at FDA, in a press conference.

In the two 12-week trials that compared varenicline with bupropion (150 mg twice daily, a combined 44% of subjects taking Varenicline were smoke free during the final 4 weeks of the trial, compared with 30% of bupropion-treated subjects and 17% of placebo-treated subjects. In one of those trials that followed up on the subjects, 22% of Varenicline-treated individuals were still smoking abstinent at a year, compared with 16% of bupropion subjects and 10% of placebo subjects.

Subjects in those studies had, on average, smoked 21 cigarettes a day for 25 years. Smoking abstinence was monitored in the trials by self-report and with weekly expired carbon monoxide testing. Notable side effects of the drug in the trials included nausea (30% of patients in one trial), insomnia, and vivid dreams. The nausea was transient and considered mild to moderate. The important point about the nausea and other side effects is that they were generally not bothersome enough that subjects quit their regimen, and a rate of 30% for nausea is not out of line with what is seen in trials of bupropion and other smoking-cessation agents, Dr. Hughes noted. Only 10% of subjects quit Varenicline because of side effects.

Varenicline is the first drug specifically designed for nicotine dependence; bupropion, though approved for smoking cessation, is an antidepressant.

Varenicline is a novel selective nicotinic receptor partial agonist, and as such, it not only eases withdrawal craving but also partially blocks the nicotine effect of smoking. This second property interferes with the reinforcement a smoker gets from lighting up, a benefit that thwarts the potential for relapse, both Dr. Hughes and FDA's Dr. Rosebraugh noted.

The capsules will be sold in two strengths, 0.5 mg and 1.0 mg. In a statement, Pfizer said it will provide patients with a personalized support program.

In a secondary analysis of the trials that included bupropion presented at the Society for Research on Nicotine and Tobacco annual meeting this year, Pfizer researchers said they did have evidence that varenicline had an impact on more measures of the reinforcing effect of smoking than bupropion and placebo.

They reported that, based on answers to a questionnaire, varenicline had a statistically significant effect over placebo in four domains of reinforcement, while bupropion had an effect over placebo in only one.

The new drug has not been specifically compared with the nicotine patch. However, in a study conducted by Dr. Hughes, the rate of tobacco abstinence was 39% at 12 weeks for a 42-mg nicotine patch and 24% for a 21-mg patch (Nicotine Tob. Res. 1999;1:169-74).

BY TIMOTHY F. KIRN

Sacramento Bureau