Cytisinicline

Whether present in electronic or combustible cigarettes, nicotine is a highly addictive substance. Dr Cindy Jacobs, chief medical officer of Achieve Life Sciences discusses the potential of cytisinicline therapy for smoking cessation.

Although e-cigarettes are considered a less dangerous alternative to combustible cigarettes, they can still result in, or sustain, nicotine addiction, for which the long-term safety issues and associated health risks are unknown.

A recent study showed that current nicotine e-cigarette users who were ex-smokers remained nicotine dependent and had higher nicotine dependence scores if they used e-cigarettes for a longer period of time or if they used more advanced nicotine e-cigarettes (related to size, battery powered, controls, etc.). These results underscored the role that e-cigarettes play in prolonging nicotine use and dependence. Despite the large and growing population of e-cigarette users, there are no nicotine cessation therapies specifically designed to support those who wish to quit e-cigarettes.

E-cigarettes can reduce or eliminate exposure to many of the toxic chemicals present in combustible cigarette smoke and are therefore potentially beneficial in reducing health risks in smokers when used as a replacement for their combustible counterpart. However, despite this potential benefit, e-cigarettes continue to deliver nicotine and are therefore not without their own health risks. Recent and ongoing studies on the health effects of nicotine containing e-cigarettes show correlations with cardiovascular disease, irreversible lung damage and respiratory disease including emphysema, chronic obstructive pulmonary disease, chronic bronchitis, and asthma.

Despite these health concerns, the use of e-cigarettes and nicotine addiction continues to grow, with approximately 13.7 million users in the United States alone in 2018.This large number of e-cigarette users creates a significant market need for vaping cessation therapy.

Many experts and professional societies recommend that smokers who switch to e‑cigarettes to reduce harm should eventually aim to stop their nicotine addiction by stopping e-cigarette use as well. Current trends show that users of e-cigarettes have a desire to quit their nicotine addiction. An online survey of approximately 500 users of nicotine vaping devices or e-cigarettes found that 73% respondents indicated that they intended to quit nicotine vaping within the next 3 to 12 months, and 27% indicated that they expected to make a quit attempt in the next three months.

"Despite these health concerns, the use of e-cigarettes and nicotine addiction continues to grow, with approximately 13.7 million users in the United States alone in 2018"

A recent publication, as a part of the Population Assessment of Tobacco and Health (PATH) comprehensive survey, reported that the majority of the 1968 established e-cigarette users surveyed expressed interest in eventually quitting nicotine vaping. Former cigarette smokers had the highest levels of intention to quit and interest in quitting vaping followed by dual users and never smoked users. The conclusion was that there is an urgent need for development of interventions to help individuals quit nicotine vaping regardless of their past or current cigarette smoking status.

Unfortunately, success rates for smoking cessation without treatment assistance are low with fewer than 10% of smokers successfully quitting in a year. Higher rates occur with FDA-approved treatment therapies developed for users of combustible cigarettes. However, the adoption rate of these treatment therapies among those who wish to quit e-cigarette use has been quite low, largely due to the unacceptable side effect profiles associated with these non-nicotine replacement therapies. New solutions for nicotine cessation, including for both combustible and e-cigarette nicotine use, that offer more favourable treatment profiles and meet consumer adoption requirements are clearly needed.

One therapy that could offer hope for smoking cessation – including cessation of e-cigarette use - and nicotine addiction is cytisinicline, a natural plant-derived product with chemistry similar to nicotine. Cytisinicline is currently being evaluated in clinical studies as a smoking cessation therapy. It has been used as a smoking cessation therapy in Central and Eastern Europe for several decades and is now being developed for use in the United States.

While recent and ongoing studies of cytisinicline have focused on users of combustible cigarettes, preliminary research indicates that this natural, plant-based therapy is also appealing to former users of combustible cigarettes who remain using e-cigarettes.

Results of clinical studies have shown those receiving cytisinicline treatment experience significantly less nausea, headaches, and abnormal dreams compared to existing treatments, offering a more tolerable side effect profile.

Additionally, a Phase 2b clinical trial (ORCA-1) found that smokers treated with cytisinicline showed a greater reduction in cigarettes smoked compared with placebo and that cytisinicline was safe and well tolerated with no serious adverse events reported.

Statistically significant quit rates were observed in the subjects treated with cytisinicline at the end of a 25-day treatment period and for an additional four-week untreated follow-up period. A pivotal trial (ORCA-2) is currently enrolling adult smokers to evaluate a longer six-week treatment period for higher cessation rates and a 12-week treatment period to potentially reduce relapse rates.

If these trials proceed, they would be the first to evaluate a nicotine cessation therapy in this patient population, which may have quitting needs and challenges distinct from combustible cigarette users. While e-cigarettes can be an important tool for reducing health risks associated with combustible cigarette use, health care providers should strive to help their patients further improve their long-term health by reducing their nicotine addiction.

About the author

Dr Cindy Jacobs is president and chief medical officer of Achieve Life Sciences. She is an experienced executive in drug development and has over 30 years’ experience in the biotechnology and pharmaceutical industry. Prior to joining Achieve Life Sciences in 2017, she served as OncoGenex’s executive vice president and chief medical officer since August 2008, and had been executive vice president and chief medical officer of OncoGenex Technologies Inc. from September 2005 to August 2008.