FDA Grants Breakthrough Therapy to Cytisinicline for E-Cigarette Nicotine Dependence

Achieve Life Sciences, Inc., a late-stage pharmaceutical company dedicated to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for cytisinicline for nicotine e-cigarette, or vaping, cessation. This designation is based on results from the Phase 2 ORCA-V1 trial, which demonstrated that treatment with cytisinicline more than doubled the odds of quitting e-cigarettes compared to placebo.

Dr. Cindy Jacobs, President and Chief Medical Officer of Achieve, emphasized the significance of this development, noting that there are currently no FDA-approved medications specifically indicated for nicotine vaping cessation. This creates a potential for cytisinicline to become a pioneering treatment for the over 13 million people in the United States who are addicted to nicotine through vaping. Dr. Jacobs expressed hope that the Breakthrough Therapy Designation would facilitate increased communication and guidance from the FDA, enabling quicker and more efficient advancement of cytisinicline as the first approved pharmacotherapy for vaping cessation, potentially extending to adolescents in the future.

The Breakthrough Therapy Designation aims to expedite the development and review of drugs intended to treat serious conditions, especially when preliminary clinical evidence suggests the drug may offer substantial improvements over existing therapies. This designation offers product sponsors the opportunity to engage with an FDA cross-disciplinary project management team, fostering interactive communication with senior managers and expert reviewers.

Achieve plans to hold an End-of-Phase 2 meeting with the FDA’s multidisciplinary team under this designation before the year ends. The FDA regards tobacco dependence as a serious or life-threatening condition, with long-term e-cigarette use also being recognized as a serious condition due to potential health risks such as respiratory and cardiovascular issues. The concern extends to adolescent and young adult use, given the potential risks to brain development and the strong likelihood of nicotine addiction, as highlighted in ‘The Report of the Surgeon General on E-Cigarette Use Among Youth and Young Adults’.

The Phase 2 ORCA-V1 trial, recently published in the Journal of the American Medical Association (JAMA) Internal Medicine, assessed the efficacy and safety of 3 mg cytisinicline administered three times daily for 12 weeks compared to a placebo in 160 adults who used nicotine e-cigarettes, did not smoke, and wanted to quit vaping. Results showed that participants treated with cytisinicline were 2.6 times more likely to have quit vaping compared to those receiving a placebo. Furthermore, a consistent trend favoring cytisinicline was observed across secondary endpoints, evaluating abstinence during and beyond the treatment period. Like in Phase 3 trials for smoking cessation, cytisinicline was well tolerated with no serious adverse events reported and excellent compliance rates.

The ORCA-V1 clinical study was supported in part by the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) through grant funding totaling $2.8 million. Achieve remains focused on addressing the global smoking health and nicotine addiction epidemic through the development and commercialization of cytisinicline. The company aims to provide a solution for the approximately 29 million adults in the United States who smoke combustible cigarettes and over 11 million adults who use e-cigarettes.

Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor and is believed to aid in treating nicotine addiction by reducing withdrawal symptoms and decreasing the reward and satisfaction associated with nicotine products. While it is an investigational product still under development and has not yet been approved by the FDA for any indication in the United States, Achieve continues to work towards its development for the treatment of nicotine addiction.