DALLAS — The first agent from a new drug class was safe and effective in helping patients stop smoking in three phase III studies that involved more than 3,000 patients.
Treatment with varenicline, a selective nicotinic acetylcholine-receptor partial agonist, led to smoking quit rates that doubled what was achieved with bupropion (Zyban, GlaxoSmithKline) and quadrupled the rate with placebo in a pair of acute therapy studies, Serena Tonstad, M.D., reported at the annual scientific sessions of the American Heart Association.
The third study showed that 24 weeks of treatment with varenicline was safe and better maintained abstinence from smoking, compared with a 12-week course of the drug.
All of the studies were sponsored by Pfizer Inc., which is developing the drug and plans to market it as Champix. The phase III data presented at the meeting were part of a new drug application submitted to the Food and Drug Administration in November, according to a statement released by Pfizer. Dr. Tonstad has received honoraria from Pfizer as a speaker and a consultant.
On the basis of the results, varenicline “was effective and appeared safe,” said Erika S. Froelicher, Ph.D., a specialist in smoking cessation and a professor of nursing and epidemiology at the University of California, San Francisco. “We can feel confident that help is on the way as we await this promising new drug,” said Dr. Froelicher, who was not involved in these studies and reported no financial relationships.
Varenicline was designed by researchers as a nonnicotine agent that is both an antagonist and partial agonist for the nicotine receptor. As an antagonist, the drug prevents nicotine from binding to its receptor, thus reducing the positive reinforcement that usually accompanies smoking and “breaking the cycle of addiction,” said Dr. Tonstad, department of preventive cardiology, Ullevål University Hospital, Oslo.
The drug's agonist side means that it also partially activates the nicotine receptor, which blunts withdrawal symptoms and curbs craving after patients stop smoking.
The two acute treatment studies had an identical design and were done at centers in the United States. Each study included slightly more than 1,000 people who smoked about a pack of cigarettes daily and had smoked for about 25 years. All the participants were motivated to quit.
They were randomized to treatment with 1-mg varenicline b.i.d., 150-mg bupropion b.i.d., or placebo. After receiving their assigned agents for 7 days while continuing to smoke, the participants were told to stop smoking on day 8. Treatment continued for another 11 weeks, during which they had weekly examinations and attended brief weekly motivational support sessions that focused on the behavioral aspects of cessation.
Successful cessation was defined as not inhaling even a single puff of cigarette smoke during the last 4 weeks of treatment. Abstinence was monitored during weekly clinic visits by expired carbon monoxide levels.
In both studies, during weeks 9–12 of treatment, 44% of those in the varenicline group abstained from smoking, as did 30% of those in the bupropion group and 18% of those in the placebo group.
Statistical analysis calculated that the odds ratio of smoking cessation was nearly fourfold higher in the varenicline group than in placebo patients, and nearly twice as high in the varenicline group than in those receiving bupropion—the only drug approved in the United States for smoking cessation. All of the rate differences between the varenicline and comparator groups were statistically significant.
A secondary end point for both studies was the rate of confirmed, continuous abstinence during the 44-week period starting with the ninth week of treatment and continuing to 1 year after the study's start. (Participants were treated for the first 4 weeks and during weeks 9–12, and then were off treatment for the next 40 weeks.)
Abstinence rates during this period were about 22% for the varenicline-treated people in both studies, compared with a 16% rate in those treated with bupropion and about 9% in those who got placebo.
The third study, done in the United States and at sites in other countries, began with 1,927 people who received 1-mg varenicline b.i.d. on an open-label basis for 12 weeks. At the end of this period, 1,236 (64%) patients remained abstinent from smoking and were eligible for the maintenance phase. The second half of the study randomized 602 people to continue to receive varenicline for a second 12-week period, and 604 were randomized to placebo.
During weeks 13–24, continuous abstinence from smoking was achieved at a rate of 71% in the varenicline group and a rate of 50% in the placebo group, a statistically significant difference. From week 13 to 52, the abstinence rates were 44% in the group treated for 24 weeks, compared with a 37% in those treated for 12 weeks. The results showed that a second 12-week course of varenicline was better than placebo for helping people stay off cigarettes, said Dr. Tonstad, who is also a professor of nutrition at the University of Oslo.