Cytisinicline Shows Statistically Significant Smoking Cessation Results in Phase 3 Trial of Adult Smokers

Topline results from the phase 3 ORCA-2 trial of cytisinicline demonstrated significantly better quit rates than placebo in smoking cessation among adult smokers.

The trial was designed to evaluate the efficacy and safety of 3 mg cytisinicline dosed 3 times daily for a period of 6 weeks or 12 weeks compared to placebo in 810 adult smokers. The subjects were monitored for smoking abstinence for 24 weeks post randomization and received standard behavioral support for the duration of the trial.

As for the primary endpoints, both the 6- and 12-week cytisinicline treatments demonstrated significantly better quit rates than placebo, with odds ratios of 8.0 and 6.3, respectively, according to the study.

Participants who received 12 weeks of cytisinicline treatment had 6.3 times higher odds to have quit smoking during the last 4 weeks of treatment versus participants who received placebo. Their abstinence rate during weeks 9 to 12 was 32.6% for cytisinicline compared to 7.0% for placebo.

Participants who received 6 weeks of cytisinicline treatment had 8 times greater odds of quitting smoking during the last 4 weeks of treatment compared to subjects who received placebo. Their abstinence rate during weeks 3 to 6 was 25.3% for cytisinicline compared to 4.4% for placebo.

The ORCA-2 participants were an average 54 years of age, smoked approximately 20 cigarettes per day at baseline, and had a median smoking history of 38 years with 4 prior quit attempts.

“Cytisinicline demonstrated impressive efficacy for smoking cessation compared to placebo in this trial, the first large randomized clinical trial conducted in a US population,” said Nancy Rigotti, MD, professor of medicine at Harvard Medical School, and principal investigator of ORCA-2, in a press release. “The trial is also notable as the first one to test the long-term efficacy of a new cytisinicline dosing schedule that has not previously been tested in a large population.”

Cytisinicline was well-tolerated with no treatment-related serious adverse events (AEs) reported. The most commonly reported AEs for placebo, 6-week cytisinicline, and 12-week cytisinicline were insomnia, abnormal dreams, headaches, and nausea.

“These strongly positive results are extremely encouraging, and we are thrilled for the successful quitters, whom after decades of smoking and multiple attempts, were finally able to kick the habit thanks to cytisinicline and the ORCA-2 trial,” said John Bencich, CEO of Achieve Life Sciences, in a press release. “These data confirm that cytisinicline, if approved by the FDA, has the potential to become the first new agent approved in nearly two decades and an important treatment option for smoking cessation, which is much needed given the limitations, particularly the significant side effects associated with existing agents. We would like to thank the investigators, healthcare providers, and subjects whose commitment and efforts to ORCA-2 made this trial a success.”

REFERENCE

Achieve Life Sciences Announces Successful, Statistically Significant Smoking Cessation Results in Phase 3 ORCA-2 Clinical Trial of Cytisinicline in Adult Smokers. GlobeNewswire. April 27, 2022. Accessed April 29, 2022. https://www.globenewswire.com/news-release/2022/04/27/2430191/0/en/Achieve-Life-Sciences-Announces-Successful-Statistically-Significant-Smoking-Cessation-Results-in-Phase-3-ORCA-2-Clinical-Trial-of-Cytisinicline-in-Adult-Smokers.html