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Achieve Life Sciences, Inc. Presents Comprehensive Long-Term Safety Data from ORCA-OL Study
Achieve Life Sciences, Inc. announced the presentation of comprehensive long-term safety data from the ORCA-OL study at the American Thoracic Society 2026 Annual Meeting. The ORCA-OL trial, an open-label, long-term, exposure safety study, enrolled 475 adults who smoke cigarettes, use e-cigarettes, or both. Participants received cytisinicline 3 mg three times daily for up to 52 weeks of continuous exposure, with a median cumulative duration of 361 days. This final clinical dataset completes the comprehensive evidence package supporting Achieve's New Drug Application (NDA), demonstrating that cytisinicline maintains a favorable safety profile across extended treatment duration in a diverse population of adults with nicotine dependence. ORCA-OL is the first long-term safety study of cytisinicline in adults using combustible cigarettes, e-cigarettes, or both — extending the clinical safety dataset well beyond the 6- and 12-week treatment durations evaluated in the pivotal Phase 3 ORCA-2 and ORCA-3 trials. The 52-week exposure findings support the long-term tolerability of cytisinicline in adults with nicotine dependence. The ORCA-OL trial included smokers (84.6%), e-cigarette users (12.8%), and dual users (2.5%), adding to the growing safety database for multiple types of nicotine dependence. Among the participants, 66.3% experienced one or more treatment-emergent adverse events, the majority of which were considered unrelated or unlikely to be related to cytisinicline by the investigator. Notably, 94.8% of these adverse events were mild or moderate in severity, with serious adverse events reported in only 6.5% of participants. No new safety signals were identified by the independent Data Safety Monitoring Committee. The most commonly reported adverse events were abnormal dreams (8.4%), insomnia (8.4%), and upper respiratory tract infection (6.7%). The incidence of nausea was 2.5%, consistent with the nausea rates observed across the Phase 3 program, and only 5.7% of participants discontinued the trial due to treatment-related adverse events. Cytisinicline will be the subject of a dedicated oral symposium presented by Nancy Rigotti, MD, Professor of Medicine at Harvard Medical School and Associate Chief for Academic Advancement in the Division of General Internal Medicine at Massachusetts General Hospital. Scientific Tobacco Action Committee Scientific Symposium — “For the First Time in Forever”: Cytisinicline, a New Medication for Nicotine Dependence. Wednesday, May 20 — 8:30-8:45 AM ET. Additionally, Mark Rubinstein, MD, Chief Medical Officer of Achieve, will present comparative effectiveness data in a poster discussion session at ATS. Poster Discussion Session — Comparative Effectiveness of Cytisinicline and Varenicline for Smoking Cessation: A Matching-Adjusted Indirect Comparison (MAIC). Wednesday, May 20 — 11:00 AM-1:00 PM ET. There are approximately 25 million adults in the United States who smoke 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. In addition, there are nearly 18 million adults in the United States who use e-cigarettes, also known as vaping. In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes. There are no FDA-approved treatments 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. Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation 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. Cytisinicline is an investigational product candidate being developed as a treatment of nicotine dependence for smoking cessation and has not been approved by the FDA for any indication in the United States. In September 2025, the company 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 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.