Anticipating Cytisinicline: First New Smoking Cessation Aid in Over 20 Years

The United States Food and Drug Administration (US FDA) is set to make a decision on cytisinicline (Achieve Life Sciences), a plant-derived partial nicotinic acetylcholine receptor agonist submitted for approval as a smoking cessation pharmacotherapy, on June 20, 2026. If approved, it would be the first new FDA-approved pharmacotherapy for smoking cessation since varenicline received approval in 2006.

David Hill, MD, a pulmonologist with Waterbury Pulmonary Associates in Waterbury, Connecticut, and Chair of the American Lung Association National Board, spoke with HCPLive ahead of the decision. He described the current landscape as one where all 7 approved smoking cessation agents are now generic, keeping costs down but removing commercial incentive to actively promote them — shifting clinical focus toward treating the consequences of smoking rather than preventing them.

"Having more options is always good," Hill said. "When somebody fails a quit attempt or doesn't tolerate a particular agent, having another thing to add to the armamentarium is a good thing."

Cytisinicline acts as a partial agonist at the α4β2 nicotinic acetylcholine receptor — the same target as varenicline, which was itself developed using cytisine as a structural template. Hill noted that the available clinical trial data show a favorable safety profile, with quit rates in the 15–20% range. While not dramatic in absolute terms, he framed that figure in clinical context: cold-turkey cessation yields approximately 5% sustained abstinence in the literature, making a 3- to 4-fold improvement meaningful, and the average smoker requires multiple quit attempts before succeeding.

He also pointed to the decades-long real-world experience with cytisine — the same base compound — in Eastern Europe and roughly 30 other countries including the UK, Canada, and Germany as an additional layer of reassurance. "There is real-world experience with a similar compound that shows good safety and efficacy," Hill said. "It's not like a new agent that's gone through clinical trials but nobody's actually used it in the real world."

Beyond smoking, cytisinicline holds FDA Breakthrough Therapy designation for vaping cessation, an indication for which no approved pharmacotherapy currently exists. Hill called the unmet need significant. Vaping was initially positioned as a cessation tool but has instead introduced nicotine dependence to a new generation, and devices can deliver nicotine at concentrations far exceeding those in conventional cigarettes. In the absence of approved vaping cessation agents, clinicians currently rely on off-label use of smoking cessation therapies. Hill said formal approval of an agent with dedicated vaping cessation data would carry practical value beyond efficacy — including facilitating insurance coverage.

Hill also underscored that pharmacotherapy alone is rarely sufficient, recommending that any quit attempt be paired with counseling and structured support. The American Lung Association's Freedom From Smoking program is available online at lung.org for patients without access to local cessation programs.

Hill had no relevant disclosures to report.

References

1. Achieve Life Sciences. Achieve Life Sciences announces FDA acceptance of cytisinicline new drug application for treatment of nicotine dependence for smoking cessation [press release]. September 3, 2025. https://ir.achievelifesciences.com/news-releases/news-release-details/achieve-life-sciences-announces-fda-acceptance-cytisinicline-new

2. Walker N, Howe C, Bullen C, et al. Cytisinicline for smoking cessation: the ORCA phase 3 replication randomized clinical trial. JAMA Intern Med. 2025;185(6):648–655.