Cytisinicline treatment increases likelihood of smoking cessation: ORCA-2 topline results

Cytisinicline resulted in clinically robust and significant improvements in smoking cessation over 6 and 12 weeks of treatment compared with placebo, according to topline results from the ongoing phase 3 ORCA-2 trial.

The ORCA-2 trial was designed to evaluate efficacy and safety of 3 mg cytisinicline (Achieve Life Sciences) three times daily for 6 weeks or 12 weeks compared to placebo. The trial enrolled 810 adult smokers (mean age, 54 years) who were monitored for smoking abstinence for 24 weeks following randomization to cytisinicline or placebo. Participants also received behavioral support during the trial.

Topline results were released via press release from the company.

“Cytisinicline demonstrated impressive efficacy for smoking cessation compared to placebo in this trial, the first large randomized clinical trial conducted in the U.S. population,” Nancy Rigotti, MD, professor of medicine at Harvard Medical School, said in the 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.”

At 12 weeks, participants assigned cytisinicline had significantly better quit rates compared with those assigned placebo (OR = 8 and 6.3, respectively), according to the release. Those who received 12 weeks of cytisinicline had 6.3 times higher odds of smoking cessation during the last 4 weeks of treatment compared with those who received placebo (P < .0001). The abstinence rate during weeks 9 to 12 was 32.6% for the cytisinicline group compared with 7% for the placebo group, according to the release.

Those who received 6 weeks of cytisinicline had eight times higher odds of smoking cessation during the last 4 weeks of treatment compared with those assigned placebo (P < .0001). The abstinence rate during weeks 3 to 6 was 25.3% for the cytisinicline group compared with 4.4% for the placebo group, according to the release.

At baseline, participants in this trial smoked an average of 20 cigarettes per day and had a median smoking history of 38 years with four prior quit attempts, according to the release.

Secondary endpoints of the trial measured continuous abstinence after treatment through 24 weeks. Both the 6- and 12-week secondary endpoints showed significantly better quit rates for participants assigned cytisinicline compared with placebo. The continuous abstinence rate from week 9 to 24 was 21.1% for those assigned 12 weeks of cytisinicline compared with 4.8% for those assigned 12 weeks of placebo (OR = 5.3; P < .0001) and the continuous abstinence rate from week 3 to 24 was 8.9% for those assigned 6 weeks of cytisinicline compared with 2.6% for those assigned 6 weeks of placebo (OR = 3.7; P = .0016), according to the release.

Cytisinicline treatment was well tolerated and no treatment-related serious adverse events were reported.

“The ORCA-2 data provide randomized phase 3 evidence that cytisinicline is a safe and effective cessation medication that resulted in the increased likelihood of abstinence by six to eight times compared to placebo,” Cindy Jacobs, MD, PhD, president and chief medical officer at Achieve Life Sciences, told Healio. “For the first time in 20 years, cigarette purchases have increased during the COVID-19 pandemic, and more than 30 million Americans continue to smoke. It is now more important than ever to bring forward new treatments to help smokers quit.”