SEATTLE and VANCOUVER, British Columbia, May 19, 2026
Achieve Life Sciences announced positive long-term safety data from the ORCA-OL study evaluating cytisinicline, its investigational plant-based therapy for nicotine dependence and smoking cessation. The data, presented at the American Thoracic Society 2026 Annual Meeting, demonstrated that cytisinicline maintained a favorable safety and tolerability profile over 52 weeks of continuous exposure in adults who smoke cigarettes, use e-cigarettes, or both. The ORCA-OL findings complete the company’s clinical evidence package supporting its New Drug Application (NDA) for cytisinicline, positioning the therapy as a potential new treatment option for nicotine addiction and smoking cessation. Importantly, the long-term study identified no new safety signals, while rates of nausea — a common reason patients discontinue smoking cessation therapies — remained notably low at just 2.5% over one year of treatment exposure.
ORCA-OL Study Strengthens Cytisinicline’s Regulatory Package
The ORCA-OL study was designed as an open-label, long-term exposure safety trial enrolling 475 adults with nicotine dependence, including cigarette smokers, e-cigarette users, and dual users. Participants received cytisinicline 3 mg three times daily for up to 52 weeks, with a median cumulative treatment duration of 361 days. According to Achieve Life Sciences, the study extends the safety database significantly beyond the six- and twelve-week treatment periods evaluated in the pivotal Phase 3 ORCA-2 and ORCA-3 trials.
The trial population included 84.6% cigarette smokers, 12.8% e-cigarette users, and 2.5% dual users, expanding the understanding of cytisinicline’s safety profile across different forms of nicotine dependence. While 66.3% of participants experienced at least one treatment-emergent adverse event, the majority were considered unrelated or unlikely to be related to cytisinicline. Notably, 94.8% of adverse events were mild or moderate, and serious adverse events occurred in only 6.5% of participants. The most commonly reported side effects included abnormal dreams, insomnia, and upper respiratory tract infection.
One of the most clinically significant findings involved the low rate of nausea, reported in only 2.5% of participants, consistent with rates previously observed in Phase 3 studies. Nausea is widely recognized as a major barrier to adherence with existing smoking cessation therapies such as varenicline, making the low incidence particularly relevant for long-term patient compliance. Additionally, only 5.7% of participants discontinued treatment due to treatment-related adverse events, further supporting cytisinicline’s tolerability during prolonged use.
Cytisinicline Advances Toward Potential FDA Approval
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Achieve executives emphasized that the ORCA-OL dataset represents a major milestone in the company’s regulatory strategy. According to the company, the complete clinical package now supports the pending NDA review by the U.S. Food and Drug Administration (FDA). The FDA accepted the cytisinicline NDA for review in September 2025 and assigned a PDUFA target action date of June 20, 2026.
Cytisinicline is being developed as a treatment for nicotine dependence and smoking cessation in adults, including both traditional cigarette users and individuals who use e-cigarettes or vaping products. The therapy works as a plant-based alkaloid that binds selectively to nicotinic acetylcholine receptors in the brain, helping reduce nicotine cravings while decreasing the rewarding effects associated with smoking and vaping.
The company highlighted the growing unmet medical need in nicotine addiction treatment. Despite millions of adults continuing to smoke or vape, there are currently no FDA-approved therapies specifically indicated for e-cigarette cessation. Cytisinicline has also received Breakthrough Therapy designation from the FDA for vaping cessation, underscoring the agency’s interest in new treatment approaches for nicotine dependence.
Additional cytisinicline data presentations at ATS 2026 include a dedicated symposium led by Nancy Rigotti discussing cytisinicline as a new treatment for nicotine dependence, as well as comparative effectiveness data evaluating cytisinicline versus varenicline for smoking cessation outcomes. If approved, cytisinicline could become one of the first major new smoking cessation therapies introduced in years, potentially reshaping treatment options for millions of individuals struggling with nicotine addiction.
Source: Achieve Life Sciences press release
