Smoking Cessation Drug May Offer Lower-Cost Option

Liam Davenport

December 18, 2014

The plant-derived drug cytisine is superior to nicotine replacement therapy (NRT) in helping smokers quit for at least 1 month, New Zealand investigators have discovered.

The drug's origins can be traced back to the Second World War; the drug has been used as a smoking cessation treatment in Eastern Europe for decades. The current study suggests that it could offer a low-cost alternative to currently available smoking cessation medications, particularly in low- and middle-income countries.

Lead researcher Natalie Walker, PhD, National Institute for Health Innovation, School of Population Health, University of Auckland, New Zealand, told Medscape Medical News that the researchers expected cytisine would be approximately as effective NRT.

"That's why we chose a noninferiority trial design, which is a little bit different from a normal trial," she said. "To our surprise, what we found was that it was actually superior to nicotine replacement therapy," she said.

The study is published in the December 18 issue of the New England Journal of Medicine.

Cheap Alternative

The team conducted a pragmatic, open-label, noninferiority trial in which 1310 adult daily smokers who called the New Zealand national quit line were randomly assigned to receive cytisine for 25 days or NRT for 8 weeks. In addition, participants received low-intensity, telephone-delivered behavioral support.

At 1-month follow-up, continuous abstinence rates were significantly higher with cytisine than with NRT, at 40% vs 31%; the number needed to treat was 11. Adjusted logistic regression analysis indicated that the odds ratio of abstinence with cytisine was 1.5 (P = .003).

Cytisine was superior to NRT at 1 week, 2 months, and 6 months. Interestingly, a prespecified subgroup analysis indicated that cytisine was superior to NRT in women but noninferior in men.

Self-reported adverse events were more common with cytisine than with NRT, at 288 events among 204 participants vs 174 events among 134 participants. The majority of adverse events were self- limiting. The most common were nausea and vomiting and sleep disorders.

Hiding in Plain Site

In an accompanying editorial, Nancy Rigotti, MD, from Department of Medicine, Division of General Internal Medicine, and the Tobacco Research and Treatment Center, Massachusetts General Hospital and Harvard Medical School, Boston, said the study brings "renewed attention to cytisine, a potentially useful pharmacotherapy for smoking cessation that has been hiding in plain sight."

"My take-away is that cytisine appears in this study to be just as effective as nicotine replacement, perhaps more so, but I'm not utterly convinced by the trial," Dr Rigotti told Medscape Medical News.

"Nonetheless, it looks like it's comparable to a current medication that we have, which is good news, because we need more medicines to help smokers, and the great thing about cytisine is that it's cheap."

Previous studies, including a recent publication by West et al, compared cytisine with placebo for smoking cessation.

"The advance with this paper is that it is the first time it's been compared with a standard smoking cessation medicine to try to get some sense of if it's as good as or better than [the standard]," said Dr Rigotti.

"I'm not convinced that it's better than, but I think it's certainly an intriguing finding."

Approval Barriers

Although cytisine is not as effective as its sister-drug varenicline (Chantix, Pfizer, Inc), which is a cytisine-derived medication, it would cost a fraction of the amount if it was approved for use.

Dr Walker and Dr Rigotti therefore believe that it would be an ideal agent to reduce smoking rates in low- and middle-income countries.

However, they agree that there are a number of barriers to cytisine receiving regulatory approval and eventually being licensed for smoking cessation.

One of the major problems is that the majority of the data supporting cytisine's use was published many years ago, and in languages other than English. Furthermore, the drug has not been marketed outside of Eastern Europe.

"Nothing is stopping it coming out of those countries, other than it needs to go through regulatory approval in different countries," said Dr Walker.

However, Dr Rigotti pointed out that that may not be as easy as it sounds.

"We are in a bit of a catch-22, because in order for this to become widely available in the US or in Europe, it would have to go through a drug regulatory process, and in order for a drug to go through the drug regulatory process, you need a certain set of studies and you need to have a sponsor," she said.

"Any sponsor who would spend the money to do that would want to get their money back. The way they would do that is when the drug became licensed, they would get a period of exclusive rights to sell it.

"Then they would presumably do what every other for-profit company does, which is they would raise the price in order to get their money back," she added.

"The problem is that the standard regulatory approach to getting this on the market, at least in Europe and the US, would probably lead to us having yet another drug that is not affordable in low- and middle-income countries."

Dr Rigotti pointed out that the data for approval of drugs in low- and middle-income countries typically come from studies undertaken to obtain approval in the United States or in Europe.

"We are sort of stuck, and I think we need some out-of-the-box thinking if we want to try to move this forward," she concluded.

The study was funded by the Health Research Council of New Zealand. The authors and Dr Rigotti report no relevant financial relationships.

N Engl J Med. 2014;371:2353-62. Full text, Editorial

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