Treatment with cytisinicline shows benefit in e-cigarettes cessation for participants: Phase 2 ORCA-V1 Trial

USA: Cytisinicline use is linked to a greater chance of quitting e-cigarettes in adults compared to placebo doses and was well tolerated, findings from the Phase 2 ORCA-V1 Trial have shown.

The vaping cessation rate during weeks 9-12 was 31.8% for cytisinicline compared to 15.1% for placebo. The drug had a comparable number of adverse events to placebo.

The primary endpoint for ORCA-V1 was biochemically verified continuous abstinence from nicotine e-cigarette use, measured during the last 4 weeks of treatment. Subjects who received 12 weeks of cytisinicline treatment had 2.6 times higher odds, or likelihood, to have quit vaping during the last 4 weeks of treatment compared to subjects who received a placebo (p=0.035). The vaping cessation rate during weeks 9-12 was 31.8% for cytisinicline compared to 15.1% for placebo. A benefit in favour of cytisinicline was consistently observed across the secondary endpoints. Additionally, a cessation benefit was observed for cytisinicline across clinical trial sites and participant demographics such as age, gender, race, or whether they had smoked cigarettes in the past.

“These groundbreaking results from ORCA-V1 reaffirm our confidence that cytisinicline could be a safe and effective option to treat nicotine dependence,” said Dr. Cindy Jacobs, Chief Medical Officer and President at Achieve Life Sciences. “We believe that cytisinicline has the potential to become the first treatment for nicotine vaping cessation, offering new hope to those who want to quit e-cigarettes.”

Cytisinicline was well tolerated and no serious adverse events were reported. Similar rates of adverse events (AE’s) were observed between treatment arms (54.7% in the placebo arm vs. 50.9% in the cytisinicline arm). The most commonly reported (>5%) AEs in the placebo arm were anxiety, headache, upper respiratory tract infection, nausea, and COVID-19 infection. In the cytisinicline arm, >5% AEs reported were sleep disturbances, anxiety, headache, fatigue, and upper respiratory tract infection.

ORCA-V1 participants had an average age of 34 years and were engaged in current daily use of nicotine-containing e-cigarettes. Approximately half of the participants had previously tried to quit vaping by self-attempt methods. Subjects were stratified based on past smoking history. Approximately 72% were former smokers of combustible cigarettes, while 28% had not smoked cigarettes. Efficacy results were similar for both groups. ORCA-V1 was supported by the National Institute on Drug Abuse of the National Institutes of Health.

“This new study suggests cytisinicline, which has previously helped people to quit smoking cigarettes, may also help adults to stop using e-cigarettes, another nicotine-containing product,” said Dr. Nancy Rigotti, Professor of Medicine at Harvard Medical School, and Principal Investigator of ORCA-V1.

Tobacco use continues to be a major health concern, with an estimated 47 million adults in the United States using tobacco in some form in 2020, including an estimated 9 million adults who used e-cigarettes to vape nicotine. Many individuals have become dependent on nicotine and want to quit but have difficulty in doing so. No FDA-approved treatments have been specifically evaluated in this population and the ORCA-V1 trial is the first randomized, placebo-controlled clinical study to demonstrate successful e-cigarette cessation.

In addition to the results of this study, Achieve Life Sciences plans to announce topline results in the second quarter of 2023 from the Phase 3 ORCA-3 trial for cytisinicline as a new smoking cessation treatment in people who want to quit daily cigarette smoking but have not been able to do so using other available treatments.