Cytisinicline Demonstrates Value as Smoking Cessation Tool in People With or Without COPD

New data from a post-hoc analysis of the phase 3 ORCA-2 and ORCA-3 trials has demonstrated that cytisinicline was associated with significantly higher smoking abstinence rates compared with placebo in both chronic obstructive pulmonary disease (COPD) and non-COPD subgroups and was well-tolerated, supporting the therapy as a viable treatment for quitting smoking.1

“COPD patients in our study smoked for many years and had high levels of nicotine addiction. Importantly, we found that cytisinicline significantly increased the odds of quitting for this high-risk group, with an excellent tolerability profile. If approved, cytisinicline would be a new treatment tool for providers in improving health outcomes for millions living with COPD,” study investigator Judith Prochaska, PhD, MPH, Professor of Medicine at Stanford University, said in a statement.2

ORCA-2 and ORCA-3 were both double-blind, placebo-controlled trials wherein 1602 participants received 6 (n = 532) or 12 weeks (n = 534) of cytisinicline or placebo (12 weeks, n = 536), 145 (9.3%) of which self-reported COPD. Participants had a mean age of 52.2 years (SD, 11.7); 881 (55%) were female, 1290 (81%) were white, 269 (17%) were Black/African American and 113 (7%) were Hispanic or Latino. The analysis primarily assessed biochemically verified continuous smoking abstinence during the last 4 treatment weeks.1

Participants with COPD were older (61.5 vs 51.3 years, P <.0001), smoked longer (46.8 vs 34.7 years, P <.0001) and had greater nicotine dependence than those without (6.1 vs 5.6, P = .002), and higher levels of depression (HADS depression subscale 2.6 vs 2.0, P <.001). The investigators found that cytisinicline was associated with significantly higher smoking abstinence compared with placebo in both COPD and non-COPD subgroups. In the 6-week arm, treated participants with COPD had quit rates of 17.3% compared to 2.1% in the placebo group (odds ratio [OR, 9.7; P = .03), while treated participants without COPD had quit rates of 19.3% compared to 5.5% in the placebo group (OR, 4.1, P <.0001). In the 12-week arm, treated participants with COPD had quit rates of 19.1% compared to 2.1% in the placebo group (OR, 5.3, P = .04) for COPD while treated participants without COPD had quit rates of 32.6% compared to 8.6% in the placebo group (OR 5.2, P <.0001).1

Investigators found that cytisinicline was well tolerated with no serious treatment-related adverse events (AEs). The two most common TEAEs were insomnia and headache and rates were similar between groups.

“These data highlight the meaningful addition cytisinicline could make for COPD patients who are seeking a safe and effective way to quit smoking,” study investigator Mark Rubinstein, Head of Medical Affairs at Achieve, added.2 “For physicians, these results provide much-needed evidence supporting a well-tolerated potential new treatment option for a specific sub-population that traditionally faces significant barriers to successful smoking cessation. This publication reinforces Achieve’s commitment to improving outcomes for patients and empowering healthcare providers with new tools in the fight against nicotine dependence.”

Investigators noted that further research is needed to explore long-term outcomes of cytisinicline use in COPD patients as well as the full range of factors that may influence treatment success, including comorbid conditions and previous cessation attempts. However, they emphasized that the study provides encouraging evidence for cytisinicline to be a valuable tool in smoking cessation for individuals with COPD.

References

1. Prochaska J, Rubinstein M, Perdok R, Blumenstein B, Jacobs C. Cytisinicline for smoking cessation in individuals with self-reported COPD: a post hoc analysis of the ORCA-2 and ORCA-3 trials. Thorax. Published online September 17, 2025. doi:10.1136/thorax-2025-223880

2. Achieve Life Sciences Announces Publication in Thorax of Data Demonstrating Cytisinicline’s Potential Efficacy and Tolerability for Smoking Cessation in Individuals with COPD. News release. Achieve Life Sciences. News release. September 22, 2025. https://achievelifesciences.com/achieve-announces-thorax-publication-of-cytisiniclines-potential-efficacy-and-tollerability-for-smoking-cessation-in-individuals-with-copd/