Nicotine Vaccine: Another Option for Smoking Cessation?

Sue Hughes
November 13, 2007 (Orlando, FL) – A phase 2 study of a nicotine vaccine has shown that the highest dose tested produced antibodies against nicotine and was associated with an higher rate of smoking cessation than placebo.
In the study [1], presented here by Dr Stephen Rennard (University of Nebraska Medical Center, Omaha) at last week's American Heart Association 2007 Scientific Sessions, the highest dose of the vaccine tested was associated with a quit rate at 12 months of 16% vs 6% for placebo.
Rennard commented to heartwire that the quit rates in this study were generally similar to that achieved with other smoking-cessation aids, showing abstinence rates two- to threefold higher than placebo. "Nicotine patches and bupropion show a twofold greater quit rate than placebo, and this increases to about threefold with varenicline. So this vaccine could be regarded as another option, and the more options the better. Some people will prefer one method; others may prefer a different method. The more tools in the toolbox the better. Anything that helps will be welcome."
The vaccine is in development by Nabi Biopharmaceuticals under the brand name NicVAX. It consists of a chemical derivative of nicotine linked to a protein to induce an immune response. The idea is that the antibodies produced will bind to nicotine in the bloodstream and prevent it from crossing the blood-brain barrier and entering the brain, thus preventing the positive-sensation stimulus of nicotine, which mediates its addictive properties. Nabi suggests that the vaccine may have advantages over existing treatments because its effect is irreversible for potentially six to 12 months following vaccination as antibodies to nicotine continue to be produced by the body's immune system. This, it says, is important in view of the high relapse rates associated with smoking cessation.
"The vaccine is really very different from all of the other drugs that are available to help smoking cessation," Rennard said. "Theoretically, the other drugs are designed to work in the person's brain to affect the nicotine addiction process. But the vaccine targets the addicting drug, and it seems more appealing to attack the enemy."
In the phase 2 study, 301 participants who smoked at least 15 cigarettes a day (average 24 a day) were randomized to the nicotine vaccine or placebo. The vaccine was given by injection at two different doses (200 µg and 400 µg) in different schedules (four or five shots over a 26-week period). Smoking cessation was started one week after the second shot.
Correlation between antibody titers and quit rates
The group receiving five shots of the vaccine at the highest dose consistently showed the best results throughout the study, with quit rates of 25% after eight weeks vs 13% for those who received placebo. By one year, 16% of patients who had received five shots of the high dose were still abstinent, compared with 6% of those given placebo. Results also suggested that the five-shot high-dose group also achieved the highest antibody titers, and there was a direct correlation between antibody titers and quit rates.
Rennard said the vaccine was generally well tolerated but was associated with injection-site reactions, mild fever, and aches. Seven people dropped out of the study because of adverse reactions, but of these, only one was probably related to the vaccine and another one possibly related.
He added that a large trial would have to be performed for the vaccine to be marketed, with at least several hundred patients in each group. "We have shown preliminary evidence of efficacy, but the FDA will want more definitive evidence and more safety data," he added.
Rennard SI. A randomized placebo-controlled trial of a conjugate nicotine vaccine (NicVAX) in smokers who want to quit: 12-month results. American Heart Association 2007 Scientific Sessions; November 4-7, 2007; Orlando, FL. Abstract 3712