For smokers, a shot at quitting
JOSEPH DARMIENTO of Coatesville, Penn., once quit smoking for 13 weeks, his longest cigarette-free stretch since he got hooked as a teenager. Inspiration arrived in the form of Marine Corps boot camp, where cigarettes were strict no-no's.
Now, though, the 37-year-old computer systems administrator just can't shake his pack-a-day habit.
After trying and failing with other tools such as the nicotine patch and gum, and Zyban pills, Darmiento has signed up to help test a new kind of quit-smoking tool: a nicotine vaccine.
The hope is that the vaccine could teach his immune system to recognize nicotine in his bloodstream and keep it from entering his brain. As smoking becomes less pleasurable and less reinforcing, it might be easier for him to combat his cravings. "Once I put the physical part behind me, then I can concentrate on the mental battle," Darmiento says.
The vaccine, called NicVAX, is far from proven technology. But it has shown promise in early trials even in smokers who had no plans to quit.
In March, the Food and Drug Administration granted NicVAX's manufacturer, Nabi Biopharmaceuticals of Boca Raton, Fla., a fast-track application to help speed the drug's review process.
Now nine centers across the U.S., including UCLA, are recruiting smokers for a Phase 2 clinical trial. Initial results of the trial, funded in part by a recent $4.1-million grant to Nabi from the National Institute on Drug Abuse at the National Institutes of Health, are expected in mid-2007.
Better quit-smoking therapies are sorely needed to treat today's smokers, who appear to smoke more heavily and be more addicted than in the past, says Elbert Glover, professor of public and community health at the University of Maryland and head of the Maryland trial. This year, more than 400,000 smokers in the U.S. will die from smoking-related illnesses, according to the Centers for Disease Control and Prevention. About 70% of the 49 million adults and 6 million teenagers who smoke in the U.S. say they would like to quit, and every year about 40% of them try.
Fewer than 3% succeed.
A variety of tools are available for people who want to quit smoking. These include nicotine replacement methods, some medications and now, in trials, a nicotine vaccine.
In controlled studies, the likelihood of quitting smoking is about 1.5 to 2.5 times greater when patients use nicotine replacement therapy, and success rates may be slightly higher for some of the other methods.
• Nicotine gum Introduced in 1984, available by prescription or over the counter. Recommended dose: up to 24 pieces per day for up to 12 weeks. Common side effects: sore mouth, indigestion, headaches.
• Nicotine patch Introduced in 1991, available by prescription or over the counter. Recommended use: one patch, replaced daily, for up to eight weeks. Common side effects: skin irritation, insomnia, indigestion, abnormal dreams.
• Nicotine nasal spray Introduced in 1996, available by prescription. Recommended use: one to five times per hour for three to six months. Common side effects: nasal irritation, constipation, indigestion.
• Nicotine inhaler Introduced in 1997, available by prescription. Recommended use: six to 16 times a day for up to six months. Common side effects: irritated mouth and throat, indigestion.
• Bupropion (Zyban) Introduced in 1997, available by prescription. Recommended use: daily for seven to 12 weeks (sometimes up to six months). Common side effects: dry mouth, insomnia. Patients using bupropion are about two times more likely to quit smoking.
• Nicotine lozenge Introduced in 2002, available over the counter. Recommended use: up to 20 pieces per day for up to 12 weeks. Common side effects: sore mouth, irritated throat, indigestion.
• Varenicline (Chantix) Introduced in 2006, available by prescription. Recommended use: daily for 12 weeks (sometimes for an additional 12 weeks). Common side effects: nausea, headache, insomnia, abnormal dreams, changes in taste perception. Studies suggest patients are about four times more likely to quit when they use varenicline, but the drug is still very new.
• Nicotine vaccine (NicVAX and others in development) Now in clinical trials (www.clinicaltrials.gov/ct/show/NCT00318383). Likely use: five to six shots over a period of several months; possibly a booster shot to extend effects. Side effects: sore arm, headache and nausea, similar to those experienced with other vaccines. In one small study, 38% of smokers who got a high-dose vaccine managed to quit for at least a month. Results from the larger trial are expected next year.
— Regina Nuzzo
Scientists believe the new vaccine might help smokers such as Darmiento who haven't been able to quit with other methods.
On their own, nicotine molecules — just like those in drugs such as heroin and cocaine — are too small to trigger the body's immune system, says Dr. Victor Reus, professor of psychiatry at the UC San Francisco School of Medicine and head of the San Francisco trial. These molecules slip quickly and easily from the bloodstream into the brain, where they bind with nerve receptors and trigger a pleasurable dopamine release.
Thus, to create an effective vaccine, scientists attached nicotine molecules onto larger proteins. After injection with the vaccine, the immune system creates antibodies that specifically recognize nicotine. When a vaccinated smoker takes a drag, these antibodies attack nicotine in the bloodstream. Bound nicotine molecules, too big to cross the blood-brain barrier, are eventually eliminated harmlessly by the body.
Antibodies build up slowly, and patients get "six weeks of guilt-free smoking" after the first injection before they're instructed to quit, says Mitchell Nides, a consultant on the Los Angeles trial. "This is not a cold-turkey approach at all," he says.
Since the method targets nicotine, not the brain, researchers hope to see fewer side effects than with other pharmacological tools (see box). The antibodies could persist for months after injection, and possibly even longer with a booster shot, so the vaccine might also help guard ex-smokers against a relapse.
Using antibodies to treat drug abuse isn't new, Reus says. In the early 1970s, researchers tested monkeys with an experimental vaccine for heroin addiction. Today, new vaccines are being developed to treat addiction to heroin, cocaine, PCP and methamphetamine.
Other companies are also developing nicotine vaccines: Cytos Biotechnology of Zurich, Switzerland, which presented results of a Phase 2 clinical trial in Europe in May 2005; Xenova Group of Berkshire, England; and Prommune of Omaha, Neb.
An earlier, smaller test of NicVAX's safety included active smokers who had no plans to quit. Even so, results were surprisingly good, says Dorothy Hatsukami, professor of psychiatry at the University of Minnesota and lead author on the study's report. Thirty-eight percent of smokers in a group that received a higher dose of the vaccine quit smoking for at least a month, compared with 9% in the placebo group.
Still much remains to be studied. Researchers aren't certain if the vaccine is safe for pregnant women. And, for reasons that are still unclear, some smokers may not develop enough antibodies for the vaccine to be effective. With the new 300-patient clinical trial, scientists hope to determine what types of smokers are most likely to benefit from the vaccine.
By some measures, nicotine can be as addictive as heroin or cocaine, says Saul Shiffman, professor of psychology at the University of Pittsburgh. But research has shown that nicotine addiction also gains its strength from dozens of daily habits in a smoker's life — whether a few puffs in morning traffic or half a pack on the bar stool at night.
With the vaccine's help, Darmiento thinks he may have found a new "do-or-die" motivation to fight his nicotine battles. "I want to set the right example for my kids," says the father of two teenagers. They're not smokers yet, and Darmiento wants to make sure they stay that way. And, he adds, "I worry how long I'm going to be around to see them."
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