Cytisinicline Shows Positive Results for Smoking Cessation in Patients With Previous Cessation Attempts

Cytisinicline has shown meaningful effects in smoking cessation for patients with previous cessation attempts, Achieve Life Sciences reported in new data.¹ The drug showed improvement in nicotine dependence regardless of prior quitting activity, and results on extended use will be shared at the Society for Research on Nicotine and Tobacco.

Data analysis included information from ORCA-2 and ORCA-3 phase 3 trials, with 1602 combined participants. Participants had varying histories of smoking cessation, including previous medication trials like varenicline, bupropion, and nicotine replacement therapy. Information on number of previous cessation attempts was also collected, particularly if participants had tried 4 or more times to quit smoking. The ORCA 2 and 3 trials examined a 3 mg cytisinicline dose 3 times a day for either 6 weeks or 12 weeks, compared with a placebo.^2,3 Participants in all groups received behavioral support for smoking cessation.

Further data on the ORCA-OL study will be shared, offering insights into long-term use of cytisinicline. This study was an open-label, long-term exposure safety trial, following participants for up to a year of treatment. The long-term exposure survey collected patient-reported experience with the medication beyond the 6 or 12 week courses studied in previous clinical trials.

“In this analysis, cytisinicline helped people to quit smoking, even those individuals who had failed previous quit attempts or had used FDA-approved smoking cessation medications without success,” said Nancy Rigotti, MD, professor of medicine at Harvard Medical School and ORCA Program Investigator. She added that “many people have to try to quit several times before they become smoke-free. This finding should offer hope to patients whose prior setbacks might have discouraged them from trying to quit smoking again.”

Cytisinicline was found to benefit a range of patients with differing backgrounds of attempted smoking cessation. In published results from ORCA-2, both 6 and 12-week cytisinicline treatment showed efficacy in smoking cessation compared with placebo, along with general tolerability.²

Cytisinicline is described as a plant-based alkaloid which has a high binding affinity to the nicotinic acetylcholine receptor. Because of these interactions with nicotine receptors, the drug is believed to reduce severity of nicotine craving symptoms, thereby reducing the reward and satisfaction associated with nicotine. The medication is currently an investigational product candidate in development for treatment of nicotine dependence for smoking cessation. It is not currently approved for any indication by the US Food and Drug Administration, but it was granted National Priority Voucher status and Breakthrough Therapy designation.

“Patient experience is hugely important for those trying to quit smoking,” said Mark Rubinstein, MD, chief medical officer of Achieve Life Sciences. “It is encouraging to see trial participants describing meaningful benefits, including successful quitting and improvements in physical health. We're committed to supporting people who want to quit smoking at every stage, whether they're trying to quit for the first time or making another attempt,” he highlighted.

References

1. Achieve Life Sciences presents data at SRNT demonstrating successful cessation in smokers with extensive prior treatment exposure; and on participant experience in the ORCA-OL study. Press release. March 4, 2026. Accessed March 4, 2026. https://www.globenewswire.com/news-release/2026/03/04/3249328/0/en/Achieve-Life-Sciences-Presents-Data-at-SRNT-Demonstrating-Successful-Cessation-in-Smokers-with-Extensive-Prior-Treatment-Exposure-and-on-Participant-Experience-in-the-ORCA-OL-Study.html

2. Rigotti NA, Benowitz NL, Prochaska J, et al. Cytisinicline for smoking cessation: a randomized clinical trial. JAMA. 2023;330(2):152-160.

3. A second study of cytisinicline for smoking cessation in adult smokers (ORCA-3). ClinicalTrials.gov. January 14, 2026. Accessed March 4, 2026. https://clinicaltrials.gov/study/NCT05206370?tab=study