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Smoking Cessation Aid Cytisnicline Up for FDA Review
A form of the cytisine regimen, widely used in Eastern Europe for decades, is finally being put in front of US regulators after recently also becoming available in the UK.
Achieve Life Sciences has submitted a new drug application (NDA) for cytisnicline as a treatment of nicotine dependence for smoking cessation in adults.1
“Submitting the cytisinicline NDA represents a decade of research and is a significant milestone toward delivering a new, evidence-based potential treatment for nicotine dependence, an urgent public health challenge with few effective options,” Cindy Jacobs, MD, PhD, President and Chief Medical Officer of Achieve Life Sciences, said in a statement.1 “Smoking-related illnesses claim the lives of nearly half a million people annually in the U.S. alone, and we are committed to making an impact. We look forward to collaborating closely with the FDA during the review process and remain hopeful about the potential of cytisinicline to make a meaningful difference for patients and healthcare providers who are seeking new treatment options.”
The NDA submission is based off positive data from the phase 3 ORCA-2 and ORCA-3 trials, data from the latter of which were shared by the company in April 2025. ORCA-3 was a 3-group double-blind, placebo-controlled, replication randomized trial conducted at 20 clinical trial sites in the US from January 2022 to March 2023, with data analyses performed from May 3, 2023, to March 20, 2024.
ORCA-3 compared a novel cytisinicline regimen at 6 and 12 weeks to placebo among 792 adults who smoked 10 or more cigarettes daily and sought to quit, Participants were randomized 1:1:1 to 3-mg cytisinicline 3 times daily for 12 weeks; 3-mg cytisinicline 3 times daily for 6 weeks followed by placebo for 6 weeks; or placebo 3 times daily for 12 weeks and follow-up with behavioral support continued for 24 weeks. Cytisinicline is a plant-based alkaloid that binds to the nicotinic acetylcholine receptor with high affinity, also known as cytisine and approved as Tabex in parts of Europe.3
Smoking abstinence and smoking urges were significantly improved in the intervention groups. For 6-week treatment, 39 (14.8%) in the cytisinicline group (14.8%) were abstinent during weeks 3 to 6 as compared with 16 (6.0%) in the placebo group (odds ratio [OR], 2.9 [95% CI, 1.5-5.6]; P <.001). For 12-week treatment, 80 (30.3%) in the cytisinicline group were abstinent during weeks 9 to 12 (OR, 4.4; 95% CI, 2.6-7.3; P < .001) as compared with 25 (9.4%) in the placebo group.2
Continuous abstinence rates for the 6-week treatment were 6.8% in the cytisinicline group compared with 1.1% in the placebo group from weeks 3 to 24; furthermore, continuous abstinence rates for the 12-week treatment were 20.5% in the cytisinicline group compared with 4.2% in the placebo group for weeks 9 to 24. Furthermore, the cytisinicline group had a greater reduction in craving (−15.2 points [95% CI, −16.4 to −14.0]) than the placebo group (−12.0 points [95% CI, −13.5 to −10.5]; P <.001).2
“The Achieve NDA submission is a significant milestone in our mission to improve the health and well-being of adults who smoke, and to provide a new tool for healthcare providers to aid in the fight against nicotine dependence. The public health burden of smoking is substantial, impairing the lives of up to 29 million Americans who have few treatment options. It is a serious medical condition that has been proven to increase the risk of developing numerous comorbidities, including respiratory and cardiovascular diseases and multiple cancer types. Patients deserve a new medical solution to help address this unmet medical need,” Rick Stewart, Chief Executive Officer of Achieve Life Sciences, added.1 “We would like to express our sincere gratitude to the ORCA Program clinical trial participants and healthcare providers, as well as to our dedicated Achieve team and all those who continue to support our mission to help people live better and healthier lives by overcoming the powerful grip of nicotine dependence.”
REFERENCES
Achieve Life Sciences Announces Submission of NDA to FDA for Cytisinicline as a Treatment of Nicotine Dependence for Smoking Cessation. News release. Achieve Life Sciences. June 26, 2025.
Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA Intern Med. Published online April 21, 2025. doi:10.1001/jamainternmed.2025.0628
Wise J. NICE proposes adding cytisine as treatment option for smoking cessation. BMJ. 2024; 387: q2563. doi: 10.1136/bmj.q2563
