Cytisinicline, a Plant-Based Medication, Could Help Curb E-Cigarette Use Among Adults Patients

Nancy Rigotti, MD
Credit: Harvard T.H. Chan School of Public Health

Results of a new trial suggest cytisinicline, a plant-based medication, could help adult patients ditch their e-cigarette dependence.

Named the ORCA-V1 trial, the results of the study, which included more than 150 adult patients reporting e-cigarette use, suggest the use of cytisinicline was associated with a greater proportion of patients achieving discontinued use of e-cigarettes relative to placebo therapy at the end of the treatment period.

"Many people who use e-cigarettes want to quit but find it difficult due to nicotine dependence. They need help to stop vaping, yet no FDA-approved medication is currently available to help them do so," said principal investigator Nancy Rigotti, MD, director of the Tobacco Research and Treatment Center at Massachusetts General Hospital and professor of Medicine at Harvard Medical School. "Cytisinicline has been shown in clinical trials to be effective and safe to help adults stop smoking cigarettes. The results of this study indicate that it might also help people to quit vaping."

A partial agonist at α4β2 nicotinic acetylcholine receptors that mediate nicotine dependence, cytisinicline has shown efficacy for cigarette smoking cessation in prior research. Given the increasing popularity of nicotine e-cigarette use in the US, the ORCA-V1 trial, which was supported by the National Institutes of Health’s National Institute of Drug Abuse, was a 16-week study launched in 2022 with the intent of assessing cytisinicline, 3 mg, taken 3 times daily against placebo therapy for 12 weeks, with biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment (weeks 9-12) and through 4 weeks posttreatment (weeks 9-16) serving as the primary and secondary outcomes of interest, respectively.¹

Conducted at 5 US sites, the trial enrolled and randomized 160 adult patients who vaped nicotine e-cigarettes but did not smoke cigarettes in a 2:1 ratio to cytisinicline or placebo therapy for 12 weeks, in addition to weekly behavioral support. In total, 107 were randomized to cytisinicline and 53 were randomized to placebo therapy.¹

Investigators pointed out the overall cohort had a mean age of 33.6 (Standard Deviation [SD], 11.1) years, 51.9% were female, 3.8% were Asian, 8.8% were Black or African American, 84.4% were White, 3.1% were another race, and 5.6% were of Hispanic ethnicity. Of note, baseline characteristics were similar between both groups.¹

Of the 160 adults included in the trial, 78.8% had ever smoked a cigarette and 71.9% had smoked more than 100 cigarettes in their lifetime. Among the 160 who underwent randomization, 131 completed the trial. For the purpose of analysis, all participating with missing outcomes were counted as nonabstinence.¹

Results of the trial suggested a greater proportion of patients in the cytisinicline group achieved biochemically confirmed continuous e-cigarette abstinence during the last 4 weeks of treatment (31.8% vs 15.1%; odds ratio [OR], 2.64; 95% Confidence Interval [CI], 1.06-7.10; P = .04). Further analysis suggested a greater proportion of those in the cytisinicline group also experienced a greater rate of biochemically confirmed continuous abstinence extending 4 weeks posttreatment (23.4% vs 13.2%; OR, 2.00; 95% CI, 0.82-5.32; P = .15). Investigators highlighted additional analyses examining subgroups defined by age, sex, race, cigarette smoking history, age of first e-cigarette use, e-cigarette dependence, and e-liquid flavor used found no evidence of heterogeneity in the effect of cytisinicline on the primary outcome.¹

“As we’ve seen now in multiple clinical trials, the safety and tolerability profile of cytisinicline is very compelling and we believe it will be a key driver of compliance when approved for use,” commented Cindy Jacobs, MD, PhD, president and chief medical officer at Achieve Life Sciences.² “Many people who attempt to quit nicotine struggle with withdrawal symptoms and cravings, making it difficult to maintain abstinence. Current treatments can have high rates of headaches and nausea, and we are simply not seeing that with cytisinicline, giving us confidence that cytisinicline’s profile will help more people, who want to quit, succeed in doing so.”

In an editorial comment, Suchitra Krishnan-Sarin, PhD, andLisa M. Fucito, PhD, both of the Department of Psychiatry at Yale School of Medicine, detailed the urgency of the situation at hand regarding the rising popularity of e-cigarette use, particularly among those who have never smoked cigarettes.³

“Health care professionals and policymakers need to move beyond the current public health conundrum surrounding e-cigarettes and focus on developing optimally targeted and tailored interventions to address e-cigarette use behaviors,” wrote the pair.³ “In this regard, the trial by Rigotti and colleagues is an excellent step in the right direction.”

References:

1. Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial. JAMA Intern Med. Published online May 06, 2024. doi:10.1001/jamainternmed.2024.1313
2. Achieve Life Sciences. Achieve Life Sciences announces publication of Cytisinicline vaping cessation trial results in Jama Internal Medicine. Achieve Life Sciences. May 6, 2024. Accessed May 6, 2024. https://achievelifesciences.com/achieve-announces-publication-of-cytisinicline-vaping-cessation-trial-results-in-jama/.
3. Krishnan-Sarin S, Fucito LM. Time for a Focus on Cessation of E-Cigarettes. JAMA Intern Med. Published online May 06, 2024. doi:10.1001/jamainternmed.2024.1310