BioWorld International Correspondent
LONDON - A trial of a vaccine against nicotine has produced promising results, raising hopes that it could be used to treat smoking addiction by 2010.
Significantly more of the people whose immune systems responded most strongly to the candidate vaccine abstained from smoking cigarettes than those who received placebo injections.
A vaccine could be used to help people give up smoking, or could be given to children to prevent them from starting. Every day in the U.S., an estimated 4,000 children sample their first cigarette. There are an estimated 1.3 billion smokers worldwide, and 5 million tobacco-related deaths each year. Most smokers who try to give up fail, despite the help of therapies such as nicotine patches.
In the latest trial, the vaccine, manufactured by Cytos Biotechnology AG, of Zurich, Switzerland, was well tolerated. Up to 70 percent of those taking part in the study reported some pain and swelling at the injection site, or flu-like symptoms, but those passed within 24 hours.
Jacques Cornuz, of the University Hospital in Lausanne, Switzerland, the principal investigator, reported the results May 14 at the annual meeting of the American Society of Clinical Oncology in Orlando, Fla., on behalf of the three Swiss study centers.
He said: "I am very excited about the outcome of this study, as the data clearly suggest that antibodies against nicotine are effective in helping people quit smoking. I believe that the vaccine approach has the potential to dramatically alter the way we will treat smoking addiction in the future."
Wolfgang Renner, CEO of Cytos, told BioWorld International: "The encouraging aspect to these results is that they show a direct relation between the level of antibodies induced by the vaccine and the desired clinical outcome - in other words, continued abstinence."
He added that the trial provides proof of principle for Cytos, that it is possible to use an individual's own defenses and immune system to modulate chronic conditions. Renner said the finding was important for the 27 vaccine candidates the company has in other areas, such as high blood pressure, obesity or Alzheimer's disease.
Cytos has developed a virus-like particle called Immunodrug, which acts as a platform for antigens, presenting them in an organized display, so that they stimulate the immune system strongly. For the smoking vaccine, nicotine is covalently linked to the surface of the particle, so that each particle displays about 585 nicotine molecules.
Nicotine is the principal addictive component of tobacco. It passes across the blood-brain barrier, and stimulates neurons in the brain. In response, the neurons release a battery of neurotransmitters, including dopamine and serotonin, which satisfies the craving.
When nicotine is bound to the antibodies induced by the vaccine, the complex is too big to pass the blood-brain barrier, and prevents nicotine from stimulating the brain.
The trial included 341 healthy male and female smokers. Two-thirds received the vaccine, while the remaining third received placebo. The participants were aged between 18 and 70, and had been smoking between 10 and 40 cigarettes a day for at least three years. All wanted to quit smoking. They received five monthly injections of either vaccine or placebo.
All received counselling each time they received an injection. One month after the first injection, the volunteers were asked to make a serious attempt to quit.
Participants who received placebo injections did not produce antibodies against nicotine. The antibody response of those who received the vaccine varied. There was a highly statistically significant difference in the continuous abstinence from cigarettes between the placebo group and those with a high antibody response (p=0.004). Out of 53 people with a high antibody response, 30 (57 percent) managed to abstain from smoking for eight to 24 weeks after the start of treatment.
Renner said, "It is now our goal to get everybody into this high antibody response range." That would be done by increasing the dose and adding more injections.
Cytos now is embarking on two studies aimed at determining the optimal dose regimen in preparation for Phase III registration trials, which Renner expects will start in 2007.