Cytisinicline Shows Promise for Smoking Cessation Even in Treatment-Resistant Patients, Phase 3 Data Reveals
Key Insights
A pooled Phase 3 analysis of over 1,600 participants demonstrated that cytisinicline achieved high quit rates regardless of participants' prior use of smoking cessation medications or number of previous quit attempts.
The analysis combined data from ORCA-2 and ORCA-3 trials, showing efficacy across participants with varying histories of prior quit medications including varenicline, bupropion, and nicotine replacement therapy.
Late-breaking survey data from the year-long ORCA-OL safety study revealed positive participant experiences with extended cytisinicline use, including successful quitting and improvements in physical health.
Achieve Life Sciences announced new data demonstrating that cytisinicline, a plant-based smoking cessation treatment, delivers meaningful quitting success regardless of participants' prior use of smoking cessation medications or number of previous quit attempts. The findings were presented at the Society for Research on Nicotine & Tobacco (SRNT) 2026 Annual Meeting in Baltimore, Maryland.
Phase 3 Analysis Shows Broad Efficacy
A pooled analysis of data from the ORCA-2 and ORCA-3 Phase 3 trials examined outcomes in 1,602 participants with varying histories of prior quit medications, including varenicline, bupropion, and nicotine replacement therapy (NRT). The analysis also evaluated participants based on whether they had made four or fewer previous quit attempts versus more than four attempts.
"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 Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School, Director of Tobacco Research and Treatment Center, Massachusetts General Hospital, and ORCA Program Investigator. "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."
The data showed that 6 and 12 weeks of cytisinicline treatment delivered high quit rates across a broad range of patients, regardless of their prior quit history.
Extended Use Safety Data
Achieve also presented late-breaking survey data from ORCA-OL, an open-label, long-term exposure safety study that followed participants for up to one year of treatment. The voluntary post-trial survey provided insights into patient-reported experiences with extended cytisinicline use beyond the 6- and 12-week courses previously studied.
"Patient experience is hugely important for those trying to quit smoking," said Dr. Mark Rubinstein, 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."
Mechanism and Market Context
Cytisinicline is a plant-based alkaloid with high binding affinity to the nicotinic acetylcholine receptor (search). It is believed to aid in treating nicotine addiction by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products.
The treatment addresses a significant public health need, with approximately 29 million adults in the United States smoking combustible cigarettes. Tobacco use is currently the leading cause of preventable death, responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually. More than 87% of lung cancer (search) deaths, 61% of all pulmonary disease (search) deaths, and 32% of all deaths from coronary heart disease (search) are attributable to smoking and exposure to secondhand smoke.
Regulatory Progress
In September 2025, Achieve announced that its New Drug Application, submitted to the U.S. Food and Drug Administration (FDA) in June 2025, had been accepted for review. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of June 20, 2026. The NDA is for cytisinicline to be used as a treatment of nicotine dependence (search) for smoking cessation in adults, based on two successfully completed Phase 3 studies and its open-label safety study.
Additionally, the company has completed a Phase 2 study with cytisinicline in vaping cessation and conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication. There are approximately 17 million adults in the United States who use e-cigarettes, and no FDA-approved treatments are currently indicated specifically as an aid to nicotine e-cigarette cessation. The FDA has awarded the Commissioner's National Priority Voucher for e-cigarette or vaping cessation and granted Breakthrough Therapy designation to address this critical need.