• 10/21/2007
  • Orlando, FL
  • By Rabiya Tuma, Ph.D., MedPage Today Staff Writer
  • MedPageToday.com

A therapeutic vaccine against nicotine significantly improved smokers’ ability to quit cigarettes and avoid lighting up for six months, researchers reported here.

However, the vaccine was only effective in patients who achieved a strong antibody response to monthly injections of the vaccine, Swiss investigators said over the weekend at the American Society of Clinical Oncology meeting.

There was no statistically significant difference between the two trial arms when all patients who were available for follow-up and stayed on protocol were evaluated. Of those patients, 64 of 159 in the vaccine arm and 25 of 80 in the placebo arm (40% versus 31%; p>0.05 but the specific number was not provided) abstained from cigarettes for five months.

However, when the researchers split the participants in the vaccine arm into three equal groups, according to the intensity of their antibody response, significantly more of the individuals in the top group quit smoking compared with those in the placebo arm. Thirty of the top 53 responders (57%) abstained from cigarettes for 24 weeks, compared with 25 of the 80 patients (31%) in the placebo arm (p=0.004).

Because only strong responders gained clinical benefit, the team is now looking for ways to boost the antibody responses by altering the vaccination schedule, dosing, and vaccine adjuvant preparation, said Philippe Müller, M.D., of Cytos Biotechnology AG in Zurich, the company developing the vaccine. Müller was an author on the vaccine study.

When the investigators find a method to enhance the average antibody titers, they will move to a phase III trial, said Dr. Müller.

All participants in the current trial smoked between 10 and 40 cigarettes per day prior to the trial and had been habitual smokers for three or more years.

Patients were randomized in a 2:1 manner. All patients received monthly injections for six months and participated in regular counseling to assist them in quitting.

The vaccine is composed of a large protein aggregate that approximates the size of a virus and has nicotine on its surface. The size of the nicotine-protein particle triggers an immune response. (Without the protein carrier, nicotine is too small to be recognized by the immune system.)

At one month, researchers asked all participants to “make an honest effort to quit,” said Dr. Müller. Patients recorded their tobacco consumption in a diary and were checked at monthly visits for carbon monoxide in their exhaled air, a measure that reflects tobacco consumption in the past 24 hours.

“We know from previous cessation trials that people who are abstinent for six to 12 months can maintain on their own” after that, said Dr. Müller.

The successful rate of abstinence in the placebo arm was much higher than expected, said Dr. Müller. He attributed that to the counseling received by all participants. The American Cancer Society estimates that 5% of people who try to quit remain abstinent for three to 12 months, compared to 31% seen in the placebo arm here.

The vaccine is thought to work by binding the nicotine in a patient’s blood and blocking its access to the brain. Thus if a patient with a high antibody titer smokes a cigarette, nicotine never has a chance to induce reward signals or a sensation of pleasure in his or her brain. Without such biochemical feedback “a patient who relapses will not fall into a full relapse situation,” said Dr. Müller.

Because the mechanism of action of the vaccine is to sequester all of the nicotine in a patient’s system, individuals who use nicotine replacement products would not benefit from the therapy. Such individuals were excluded from analysis in the current trial.

“I think this is an important cancer prevention strategy,” said Vassiliki Papadimitrakopoulou, MD, of M.D. Anderson Cancer Center in Houston, who chaired the session in which the data was presented. She noted that several companies are working on anti-nicotine vaccines but this was the only group presenting data at the meeting.