Achieve Life Sciences Publishes Phase 3 ORCA-3 Trial on Smoking Cessation in JAMA Internal Medicine

Achieve Life Sciences, Inc., a company dedicated to the development of cytisinicline for nicotine dependence and smoking cessation, recently released full results from its ORCA-3 trial. These findings, published in the Journal of the American Medical Association (JAMA) Internal Medicine, come from a comprehensive Phase 3 clinical trial. This study was designed to evaluate the effectiveness of cytisinicline, a plant-based alkaloid, in aiding smoking cessation among 792 adult participants in the United States.

ORCA-3 is the second in a series of randomized, placebo-controlled Phase 3 trials focusing on cytisinicline. The trial involved adults who smoked an average of 20 cigarettes daily, with a median smoking history of 36 years and multiple previous attempts to quit. Notably, less than half of these participants had previously tried varenicline, a smoking cessation aid known for its adverse side effects, potentially highlighting cytisinicline’s appeal due to its more favorable side effect profile.

The trial investigated two treatment durations: 6 weeks and 12 weeks, with participants receiving 3mg of cytisinicline three times a day. Results showed significant enhancements in smoking cessation rates compared to the placebo group. Cytisinicline not only increased the likelihood of participants quitting smoking but also led to fewer nicotine cravings. This reduction in cravings was evident even among participants who continued smoking, as demonstrated by decreased craving scores and lower levels of cotinine, a nicotine metabolite.

One of the standout findings from the ORCA-3 trial is cytisinicline’s targeted action on nicotine receptors, which minimizes side effects typically associated with smoking cessation drugs. Cindy Jacobs, MD, PhD, President and Chief Medical Officer of Achieve Life Sciences, emphasized cytisinicline's limited off-target effects, which contribute to its high tolerability. According to Dr. Jacobs, cytisinicline selectively targets nicotine receptors and avoids interaction with other receptors that could induce nausea or gastrointestinal issues, providing a more comfortable treatment experience.

The trial underlined the significant public health challenge posed by smoking, which remains the leading cause of preventable deaths worldwide. In the United States alone, smoking accounts for a substantial number of deaths annually, outpacing other preventable causes. The trial results suggest that cytisinicline could play a critical role in smoking cessation efforts, potentially reducing the health risks associated with smoking.

Nancy Rigotti, MD, a Professor of Medicine at Harvard Medical School and Director of the Tobacco Research and Treatment Center at Massachusetts General Hospital, commented on the study's implications. She noted that the findings indicate cytisinicline could become a valuable tool in helping smokers quit, pending FDA approval. This could significantly impact public health by lowering smoking-related health risks.

Achieve Life Sciences plans to submit a New Drug Application (NDA) for cytisinicline to the U.S. Food and Drug Administration (FDA) by June 2025. The company has made significant strides in developing cytisinicline, having completed two Phase 3 trials and one Phase 2 trial focused on vaping cessation. An ongoing open-label safety study is also fully enrolled, further supporting the potential of cytisinicline as a treatment for nicotine addiction.

In conclusion, the ORCA-3 trial adds to the growing body of evidence supporting cytisinicline as an effective and well-tolerated treatment for smoking cessation. Achieve Life Sciences continues to advance its mission to address the global nicotine dependence epidemic, with cytisinicline poised to offer a promising solution for millions of smokers seeking to quit.