Achieve Life Sciences Publishes Full ORCA-3 Results In JAMA, Confirms Cytisinicline's Smoking Cessation Benefits

Achieve Life Sciences, Inc., a late-stage speciality pharmaceutical company focused on nicotine dependence treatments, has announced the complete publication of its Phase 3 ORCA-3 clinical trial results in JAMA Internal Medicine. The study evaluated cytisinicline, the company’s investigational smoking cessation therapy, in 792 U.S. adults. Findings confirmed the drug’s efficacy and tolerability over both 6- and 12-week regimens, with sustained benefits in reducing nicotine cravings and supporting long-term smoking cessation up to 24 weeks.

“Most people who smoke want to quit, and it often takes multiple attempts to do so successfully. Our trial participants were no exception and had multiple previous quit attempts. However, less than half had previously tried varenicline, possibly due to its well-known adverse event profile,” said Cindy Jacobs, MD, PhD, President and Chief Medical Officer of Achieve Life Sciences. “Cytisinicline is very selective in targeting only nicotine receptors and has shown limited binding to other off-target receptors that can cause side effects, like nausea and gastrointestinal disturbances. We believe this leads to a highly tolerable treatment with cytisinicline, as demonstrated in our clinical trial program.”

The publication builds on topline results initially shared in May 2023, offering more profound insights into cytisinicline’s mechanism of action. The compound targets specific nicotine receptors, minimising off-target effects and side effects typically seen with existing treatments. Data from ORCA-3 and its predecessor, ORCA-2, consistently show that cytisinicline significantly improves quit rates and reduces cravings, reinforcing its potential as a new standard in smoking cessation therapies. 

“More deaths each year in the U.S. are attributed to cigarette smoking than to any other preventable cause, and our current smoking cessation treatment options are limited,” said Nancy Rigotti, MD, Professor of Medicine at Harvard Medical School, Director of Tobacco Research and Treatment Center, Massachusetts General Hospital, and ORCA Program Investigator. “The study findings published today suggest that cytisinicline, if approved by the FDA, could help many smokers to quit and reduce the smoking-related risks to their health.”

Participants in the ORCA-3 trial had a median smoking history of 36 years and averaged 20 cigarettes per day at baseline. The study showed that cytisinicline not only improved the odds of quitting but also helped reduce nicotine intake for those who continued smoking, as demonstrated by lower craving scores and reduced cotinine levels. Achieve Life Sciences plans to submit a New Drug Application (NDA) for cytisinicline to the U.S. FDA by June 2025.