FDA Approves Smoking-Cessation Drug

[Angel]

The FDA today approved the smoking-cessation drug Chantix (varenicline tartrate), which targets nicotine receptors in the brain.

The approval followed a priority review that the FDA said was necessary because of the drug's "significant potential benefit to public health."

The drug, which was developed by Pfizer, effectively occupies nicotine receptors in the brain and produces effects similar to nicotine, while blocking nicotine itself from the receptors. This one-two approach is designed to prevent withdrawal symptoms while it blocking the nicotine high from cigarettes for smokers who relapse.

In a press release, Scott Gottlieb, M.D., the FDA's deputy commissioner for medical and scientific Affairs, said the Chantix approval underlines the FDA's commitment to "helping facilitate the development of products to help people quit smoking and improve their overall quality of life."

The fast FDA approval followed a somewhat chilly reception given to phase III trial results reported last November at the American Heart Association meeting in Dallas.

Serena Tonstad, M.D., Ph.D., of the University of Oslo reported then that smokers taking Chantix were more likely to be smoke-free at 12 weeks than patients taking Zyban (bupropion) or placebo. But by one year, only one in five patients treated with Chantix were still smoke free, which led a number of researchers to raise questions about the drug's staying power.

Chantix works by partially blocking the alpha4-beta2 nicotinic receptor in the brain, which Dr. Tonstad said is the main nicotine receptor. Within 10 to 19 seconds of a single puff from a cigarette, nicotine attaches to this receptor. The receptor, in turn, triggers large increases in dopamine, which rewards the smoker with a pleasurable sensation.

Chantix attaches to the receptor and by occupying the receptor it prevents nicotine from attaching, which can break the cycle of addiction by blocking the reward reinforcement associated with large increases in dopamine, Dr. Tonstad said in November. She said the drug was well tolerated with the major side-effect of nausea, but it was mild and did not cause any patient to stop taking the drug.

At the AHA Dr. Tonstad reported results from two of the six clinical trials that were considered in the FDA approval. Those two studies enrolled roughly 2,000 patients, and used the same design. Patients were randomized to Chantix (1 mg/bid.), Zyban (150 mg/bid.) or placebo.

Timothy Gardner, M.D., of Wilmington, Del., who was chairman of the AHA program committee, said at the time that the absolute numbers reported by Dr. Tonstad were "a little disappointing." He noted, for example, that the one-year cessation rate was 22.1% for the Chantix group versus 16.4% in the Zyban group and 10% in the placebo arm. He said those rates were "underwhelming" given the fact that the patients were "motivated to quit since they entered a smoking cessation study." Moreover, he pointed out that the smokers enrolled in the study were not "really heavy smokers since they smoked only about a pack a day."

The FDA said the approved course of Chantix treatment is 12 weeks. Patients who successfully quit smoking during Chantix treatment may continue with an additional 12 weeks of Chantix treatment to further increase the likelihood of long-term smoking cessation.