Smoking vaccine fails in clinical trial

Not two weeks after an experimental cocaine vaccine showed promise in helping drug addicts kick that habit, a report has been released showing that an anti-smoking vaccine has failed to reach its targets in a mid-stage study. In the year-long Phase II study, early indications showed the nicotine vaccine NIC002 couldn't achieve a statistically significant improvement in continuous abstinence from smoking in weeks 8 to 12 after the start of treatment, compared to a placebo.

Novartis (NVS), which bought the rights to the nicotine addiction vaccine from Swiss start-up Cytos Biotechnology in April 2007, will stay on-board for the duration of the trial, though the drug now seems unlikely to reach the market. Not only is the study result a blow to smokers hoping to quit; it's also a blow to Cytos, which saw its shares slammed in the Swiss market on Friday. Cytos is now unlikely to get its milestone payment from Novartis, leaving it to fend for itself. However, Cytos CEO Wolfgang Renner assured DailyFinance in an emailed statement that "The financing of our operations in the next two years are secured and are not affected by the latest results. So there are no immediate consequences from the newest result."
Once nicotine -- the psychoactive drug in tobacco products that produces dependence -- is inhaled, it travels through the bloodstream to the brain, where it stimulates certain nerve cells and produces a feeling of pleasure. Much like the cocaine vaccine, which created antibodies that could target the drug's molecules and prevent its effect on the brain, NIC002 has been shown to induce nicotine-specific antibodies that prevent nicotine from crossing the blood-brain barrier. By reducing the amount of nicotine reaching the brain, NIC002 is supposed to reduce the overall effect of nicotine on those nerve cells, minimizing the reward-inducing and addiction-driving stimulus so that abstinence can be more easily achieved and maintained.

The study, which is ongoing, involves 200 smokers who are said to be motivated to quit. While the treatment was safe and well tolerated, it failed to induce sufficiently high antibody levels, which may have led to the negative outcome. As Renner explained, "Smoking addiction is not just a habit. Nicotine acts on the reward system in the brain and by getting a reward each time a smoker inhales smoke, the smoker develops a strongly conditioned behavior. Blocking the reward is one way that may lead to abstinence. In our studies smokers also received counseling."

In a previous Cytos Phase II clinical trial, the vaccine promoted and sustained long-term abstinence from smoking in the subgroup of smokers that achieved high antibody levels upon vaccination (just like with the cocaine vaccine study). Indeed, Renner added: "We are working together with Novartis to understand the reasons for the failure in the current trial. From what I understand, it is not warranted at the present time to question the concept in itself -- it seems to be a matter of insufficient antibody responses." There may be room for improvement, he commented.

For the company, this is yet another setback; a hypertension, or high blood pressure, vaccine failed to meet its target in a mid-stage trial as reported in March and June. Following the first setback in March, Cytos nearly halved its workforce to concentrate on the partnerships with Novartis and Pfizer (PFE) that would pay it money for reaching milestones. Pfizer is also interested in Cytos' Immunodrug technology and has agreements with the biotech firm "for certain novel vaccines for a defined number of human diseases."

All hope is not lost for smokers, though. The government, through the U.S. National Institute on Drug Abuse (NIDA), announced in late September that it has granted $10 million of stimulus money to Nabi Pharmaceuticals (NABI) to fund a phase III clinical trial of an anti-smoking vaccine. Nabi's vaccine, NicVax, which has received Fast Track Designation from the U.S. Food and Drug Administration, operates much the same way as Cytos' experimental vaccine. Spending $10 million to save on some of the $193 billion yearly costs associated with smoking seems like a good investment.

Unlike Cytos' vaccine, however, NicVax successfully completed the Phase IIb proof-of-concept trial in late 2007, showing statistically significant improvement in the rates of smoking cessation and continuous long-term smoking abstinence as compared to placebo. In addition, the vaccine was safe and well-tolerated. Again, high levels of antibodies were important and the company has initiated studies regarding proper dosing in 2008.

And lest we forget the cocaine vaccine study, researchers said they hope similar vaccines could work for other addictive drugs such as heroin, nicotine and methamphetamines. Despite the setback from the Cytos study, it seems that help for smokers is not far away now.

Quick smoking facts:

  • Smoking harms nearly every organ of the body, resulting in life-threatening diseases including cancer, heart and lung diseases.
  • Worldwide, there are 1.3 billion smokers and 4.9 million tobacco-related deaths per year, making tobacco use the leading cause of preventable death in the world today.
  • An estimated 43.4 million people or 19.8 percent of all adults in the United States currently smoke cigarettes.
  • Cigarette smoking is responsible for about one in five deaths in the United States annually, or about 443,000 deaths per year.
  • An estimated 49,000 of tobacco-related deaths are the result of secondhand smoke exposure.
  • On average, smokers die 13 to 14 years earlier than nonsmokers.
  • Although nearly 75 percent of smokers in the U.S. report that they want to stop smoking, less than 5 percent who try remain tobacco-free for 3 to 12 months.
  • Withdrawal symptoms include irritability, anxiety, difficulty concentrating, increased appetite
  • Tobacco dependence is a chronic condition that often requires repeated intervention.
  • Annually, in the United States, cigarette smoking costs more than $193 billion.
  • The cigarette industry spent $13 billion total in 2005 on advertising and promotions
Read Full Story