Achieve Life Sciences Completes 52-Week Safety Dataset for Cytisinicline NDA Submission

With its clinical evidence package now complete, Achieve Life Sciences has closed the final data gap in its cytisinicline New Drug Application, presenting 52-week continuous-exposure safety findings from the ORCA-OL study at the American Thoracic Society 2026 Annual Meeting on May 19.

The ORCA-OL open-label trial enrolled 475 adults dependent on combustible cigarettes, e-cigarettes, or both, each receiving cytisinicline 3 mg three times daily for up to 52 weeks, with a median cumulative exposure of 361 days. The dataset extends the safety record well beyond the 6- and 12-week durations evaluated in the pivotal Phase 3 ORCA-2 and ORCA-3 trials, addressing a documentation requirement that FDA reviewers routinely scrutinise for chronic-use indications.

The independent Data Safety Monitoring Committee identified no new safety signals across the full exposure period. Among participants, 66.3% reported one or more treatment-emergent adverse events; 94.8% of those events were mild or moderate in severity. Serious adverse events occurred in 6.5% of participants. The most frequently reported events were abnormal dreams (8.4%), insomnia (8.4%), and upper respiratory tract infection (6.7%). Nausea, a documented adherence barrier for existing nicotine dependence pharmacotherapies, was reported in only 2.5% of participants, consistent with rates observed across the Phase 3 programme. Discontinuation due to treatment-related adverse events was 5.7%.

For regulatory affairs leads preparing the NDA package, the ORCA-OL dataset resolves the long-term tolerability question across a population that includes smokers (84.6%), e-cigarette users (12.8%), and dual users (2.5%), a breadth of exposure types that broadens the safety database and may support label language covering multiple nicotine-delivery modalities. The trial's open-label design and extended duration align with ICH E1 guidance on the extent of population exposure needed to assess clinical safety for drugs intended for chronic or long-term use.

Additional cytisinicline data were scheduled for presentation at ATS on May 20, including an oral symposium led by Nancy Rigotti, MD, of Harvard Medical School and Massachusetts General Hospital.

The completeness of the clinical evidence package positions the cytisinicline NDA for FDA review, with the 52-week discontinuation rate of 5.7% due to treatment-related adverse events serving as a measurable tolerability benchmark against which the agency's benefit-risk assessment will be anchored.

Source: Achieve Life Sciences, Inc. via GlobeNewswire, May 19, 2026. Additional data presented at ATS 2026 Annual Meeting, May 20, 2026.