Phase 3 data show cytisinicline is tolerable, effective for smoking cessation

Key takeaways:

• Nearly 33% of people who received cytisinicline were abstinent toward the end of a 12-week treatment course vs. 7% who received placebo.
• It is the first large-scale trial of cytisinicline in the United States.

A 6- and 12-week course of cytisinicline were associated with higher rates of smoking cessation compared with placebo, according to results of the phase 3 ORCA-2 trial.

Cytisinicline is a plant-based alkaloid that selectively binds to the receptor subtype that mediates nicotine dependence, reducing nicotine withdrawal symptoms, Nancy A. Rigotti, MD, a professor at Harvard Medical School and director of Massachusetts General Hospital’s Tobacco Research and Treatment Center, and colleagues wrote in JAMA. Therefore, it has the potential as a smoking cessation medication. In fact, cytisinicline is used in some European countries to do just that, but it is not licensed in the United States.

Rigotti and colleagues conducted a three-group, double-blind, placebo-controlled, randomized trial to evaluate the tolerability and efficacy of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs. placebo.

The study, which was conducted at 17 U.S. sites from October 2020 to December 2021, included 810 adults who smoked cigarettes every day and wanted to quit.

The researchers randomly assigned participants in a 1:1:1 ratio to 3 mg cytisinicline three times daily for 6 weeks (n = 269), 3 mg cytisinicline three times daily for 12 weeks (n = 270) or placebo (n = 271).

Rigotti and colleagues reported that both 6- and 12-week cytisinicline schedules demonstrated smoking cessation efficacy and excellent tolerability, offering new treatment options for nicotine dependence.

Continuous abstinence rates for the 6-week course compared with placebo were 25.3% vs. 4.4% during weeks 3 to 6 (OR = 8; 95% CI, 3.9-16.3) and 8.9% vs. 2.6% during weeks 3 to 24 (OR = 3.7; 95% CI, 1.5-10.2).

For the 12-week course of cytisinicline vs. placebo, continuous abstinence rates were 32.6% vs. 7% for weeks 9 to 12 (OR = 6.3; 95% CI, 3.7-11.6) and 21.1% vs. 4.8% during weeks 9 to 24 (OR = 5.3; 95% CI, 2.8-11.1).

Rigotti told Healio that she hopes the study “will give primary care clinicians hope that a new medication to help patients quit smoking is likely to become available, though it will take time for the FDA to review and approve the drug for marketing in the U.S.”

“In the meantime, I hope the study inspires clinicians to offer every smoker — regardless of their interest in quitting — the medications and behavioral support tools we already have available to help them to cut down or quit.”

A representative from Achieve Live Sciences told Healio that the company expects to submit a new drug application to the FDA for cytisinicline as an aid for cigarette smoking cessation among adults in the first half of 2024.

In a related editorial, Jonathan Foulds, PhD, a professor of public health sciences at Penn State University, and colleagues wrote that “it is not possible to make direct comparisons between outcomes from the new cytisinicline dosing schedule and the current most effective FDA-approved smoking cessation drug, varenicline, on the basis of this new trial because the trial did not include a varenicline comparison group.”

“However, the more than fourfold increase in the smoking cessation rate over placebo at 6 months in this trial is impressive,” they wrote. “It is ... a very positive development that another new and effective drug may be added to the limited list that clinicians and individuals who smoke can choose from to help end their deadly addiction to cigarettes.”

References:

• Foulds J, et al. JAMA. 2023;doi:10.1001/jama.2023.5939.
• Rigotti NA, et al. JAMA. 2023;doi:10.1001/jama.2023.10042.