Novel Smoking Cessation Drug Candidate
Although a half century has passed since a report from the US Surgeon General called attention to the devastating health effects of smoking, today more than 70 million Americans still smoke tobacco. Half of those who continue to smoke will die prematurely from a smoking-related illness. Tobacco-related health care costs and productivity loss approach $300 billion annually in the US. Neither nicotine replacement products (e.g., patches) nor approved non-nicotine medicines have provided safe and effective long-term treatment in the large majority of smokers trying to quit. Our novel smoking cessation agent works via a distinct mechanism from currently available therapies. Preclinical studies support the prediction that it will display an improved safety profile and prove suitable for administration over longer periods. These advantages potentially offer improved initial treatment outcomes and reduction in the rate of relapse to smoking, a critical factor in treating nicotine dependence as a chronic medical condition.
The Centers for Disease Control and Prevention reports that cigarette smoking decreases life expectancy by at least 10 years. Smoking causes about one in every five deaths in the US, corresponding to more than 480,000 annually (including nearly 42,000 from secondhand smoke). Among smokers who attempt to quit, only a small minority succeeds. Even of those who receive a prescription for a standard of care medication such as varenicline (CHANTIX) or bupropion (Zyban), roughly 80 percent relapse to smoking within one year. Known risks of these drugs include nausea and irregular heartbeat, as well as behavioral changes, depressed mood, hostility, aggression, and suicidal thoughts. There is a compelling need for a therapy that more safely and effectively assists long-lasting smoking cessation.
Wake Forest Innovations has in-licensed a next generation smoking cessation lead compound (and associated intellectual property), one that acts at nicotinic acetylcholine receptors (nAChRs) in the brain in a manner distinct from varenicline, the current standard of care for smoking cessation. Whereas varenicline competes with nicotine for binding to the brain receptors involved in smoking dependence, Wake Forest is now developing a new series of molecules that modulate in a non-competitive manner the ion channel activity of the specific nAChRs (including alpha6 receptors) involved in nicotine dependence. Evidence that a drug from within this class of compounds might have superior properties for smoking cessation comes from extensive studies in several academic centers, including Duke University, Caltech, and the University of Colorado, the latter two supported in part by two 5-year National Institutes of Health National Cooperative Drug Discovery Group awards to evaluate the role of alpha6 nAChRs in nicotine addiction. The key mechanism for cessation is consistent with inhibition of dopamine release triggered by nicotine in the brain; however, additional mechanisms are also invoked in the drug’s ability to reduce anxiety and depression in animals.
- Mid-stage preclinical drug candidate
- Mechanistic studies establish role of multiple nAChRs
- Animal models support desired target product profile; additional studies could further test potential anti-relapse activity
- GMP synthesis and IND-enabling toxicology still required
- Continuing development by faculty in the Wake Forest Comprehensive Cancer Center and the Department of Physiology and Pharmacology of the Wake Forest School of Medicine, along with Wake Forest Innovations
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John Druga, MS, MBA
Licensing Director, Technology Commercialization