Vaccine maker targets smokers
ROCKVILLE, Md. -- Let's face it. It isn't easy to quit smoking.
Most of us know people who have tried smoking cessation classes, nicotine patches, nicotine gum, the drug Zyban and even hypnosis -- and then went back to their pack-a-day habit.
Now, scientists at Nabi, a Boca Raton-based biopharmaceutical company, are working on a new approach. With financial and technical support from the National Institute on Drug Abuse, they are developing a vaccine to prevent nicotine from reaching the brain and triggering chemical reactions that cause addiction.
"You can try to quit smoking, but the addiction is always there. The desire to smoke hardly ever goes away," said Robert Naso, a Nabi senior vice president who oversees product development at company laboratories in Maryland.
Nabi, which previously specialized in collecting and providing plasma to other pharmaceutical manufacturers, now focuses its research and development efforts on creating and marketing drugs that prevent and treat infectious and auto-immune diseases.
The company has several clinical trials under way in these areas, and has four pharmaceutical products on the market. Sales of pharmaceutical and antibody products generated $234 million in 1999 for Nabi, which has 1,750 employees. It had $3.3 million in net income last year. Its stock has been trading in the $5-$6 range recently and closed on Friday at $4.88.
The idea to create an anti-smoking vaccine came, in part, from the development of an unrelated vaccine for staphylococcus infections that uses similar technology.
The key to getting someone to stop smoking is to find a way to stifle the desire. Nabi scientists believe they can accomplish that with an injectable vaccine that not only prevents nicotine molecules from passing from the bloodstream into the brain, but also prompts the immune system to create antibodies that eliminate nicotine from the body.
"It's a fascinating concept -- novel and unique," said Frank Vocci, director of the division of treatment, research and development for the National Institute on Drug Abuse. "The methods we have used to date don't really work that well. This could be a real advancement."
The institute announced in April that it had awarded Nabi a four-year grant to conduct further tests on animals, particularly those related to safety, and then conduct human trials. The first year's portion, $776,000, will be released Sept. 30.
If human trials are successful and the vaccine is approved by the Food and Drug Administration, Nic-VAX, as it is called, could be available by 2005, Naso said. The company is seeking a partner to help pay development costs that could run into the tens of millions. The partner also is needed to help sell the product in the United States, and, possibly, around the world.
"We think there's a tremendous potential market for the vaccine worldwide," Naso said. "Clearly, this would be a high-valued product, but it's far too early to talk about price."
The scope of the potential market is huge.
More than 25 percent of adult Americans, or about 50 million people, smoke cigarettes. Add to this an estimated 6 million teen-agers and more than 100,000 children under age 13, according to government figures.
About 80 percent of smokers express a desire to quit, while 35 percent actually try. Fewer than 5 percent of those who make the attempt succeed for six months or longer, according to the American Psychiatric Association.
Nabi scientists and their collaborators in Minneapolis and Houston are growing excited about the project, now that efficacy testing in mice, rats, rabbits and goats has shown the vaccine blocks nicotine from entering the brain.
"We are having discussions with the Food and Drug Administration about the safety testing," Naso said. "It appears that rats and mice probably will be sufficient. Once we get those results, we will be ready to start human trials, probably within a year."
At this point, there are no known side effects, but there is a possibility some might arise during human trials. Just how long the vaccine will work cannot be determined until it is used in humans. Booster shots might be necessary.
The idea for the vaccine stemmed from the development of another vaccine -- to protect people from staphylococcus infection, a major problem in hospitals and nursing homes. That vaccine is in a final stage of human clinical trials.
"Nic-VAX came out of the expertise we gained in developing the staph vaccine," said Ali Fattom, Nabi senior director for research. "We had developed some fairly sophisticated chemical technology, and we were looking at how else we could apply it."
With all the publicity surrounding lawsuits against the tobacco industry and an attempt by the FDA to regulate tobacco as a drug, the Nabi development team saw an opportunity in trying to counter drugs of abuse, notably nicotine.
The concept is not new. Scientific literature dating to the 1960s alludes to the process, but no such vaccines were produced. The technology simply didn't exist, Nabi scientists said.
This is how it works:
Because nicotine molecules are very tiny, they can pass easily from the bloodstream into the brain. The body doesn't even recognize them.
"These molecules are flying under the radar of the immune system," the National Institute on Drug Abuse's Vocci said.
The vaccine contains nicotine molecules bonded to protein molecules. The combination is large enough so that the body produces antibodies to this foreign substance. When a person smokes, bringing nicotine from the cigarette into the bloodstream, the antibodies bind those molecules, and, because of their size, prevent them from entering the brain. In effect, the nicotine has been neutralized.
Because the nicotine never reaches the brain, there is no reaction to the drug and no further addiction. Regular smokers probably still would experience withdrawal symptoms.
"We believe the vaccine will be most effective in people who were longtime smokers and quit recently. They are prone to relapse because they get an exaggerated response when they light up another cigarette," Vocci said. "We also see great hope in helping intermittent smokers -- adolescents and others who are not yet dependent on cigarettes."
Less likely to be helped, he said, are those who have been smoking at least two or three years, consume a pack a day and are essentially hooked on the nicotine. The prime reason: Many of these smokers don't want to quit or don't believe they can.
But Nabi scientists hope they can have an impact on that group, as well.
"Without nicotine getting into the brain, the cigarette probably won't taste very good to a longtime smoker," research director Fattom said. "It might just taste like burnt paper."
With little satisfaction from their cigarettes, even hardened smokers might be more tempted to quit the habit, he said.
Nabi officials thought they might actually interest cigarette companies in the vaccine, but the outcome wasn't encouraging. A year ago, Naso wrote to Philip Morris Companies Inc. and R.J. Reynolds Tobacco Holdings Inc., presenting an overview of the project and seeking their participation.
R.J. Reynolds never responded, and Philip Morris wasn't interested. Its assistant chief counsel, Kevin Osborne, wrote to Naso that the cigarette maker maintains a "policy of declining to review or consider submissions such as yours."
Nabi scientists also are discussing another use for the vaccine -- to prevent young people from starting to smoke. They expect this idea to breed controversy.
"There is the possibility that parents might want to have their children inoculated so they never will become hooked on cigarettes," Naso said. "It does make sense. After all, we use vaccines to protect our kids from polio and other diseases. Why not nicotine?"