C102-25 Cytisinicline for Cigarette and E-cigarette Smoking Cessation: Long-term Safety Data From the ORCA-OL Clinical Trial

Rationale

New pharmacotherapies are needed to help more adults succeed in stopping smoking cigarettes and vaping electronic (e)-cigarettes. Cytisinicline, a plant-based alkaloid, selectively binds to α4β2 nicotinic acetylcholine receptors, acting as a partial agonist to reduce nicotine craving and withdrawal symptoms, and as an antagonist to limit nicotine’s reinforcing effects. A novel cytisinicline 6- or 12-week dosing regimen (vs. placebo) significantly increased smoking abstinence among cigarette smokers in two phase 3 trials (ORCA-2 [NCT04576949]; ORCA-3 [NCT05206370]), and nicotine abstinence among e-cigarette users in a phase 2 trial (ORCA-V1 [NCT05431387]). We present safety data following long-term cytisinicline treatment in adult participants who had not achieved abstinence in those three studies and subsequently enrolled in an additional 52-week cessation trial.

Methods

The open-label ORCA-OL trial (NCT06435221) enrolled current cigarette smokers and/or nicotine e-cigarette users who sought to quit and had participated in the US-based ORCA-2, ORCA-3, or ORCA-V1 studies. Patients received cytisinicline 3 mg three times daily (TID) for up to 1 year with monthly behavioral support. Safety outcomes were treatment-emergent adverse events (TEAEs).

Results

475 patients (median age 55.0 years [range 22.0-79.0]; 57.9% female; 81.3% White) received at least one dose of study medication. At baseline, participants smoked a mean of 19.4 (SD 10.2) cigarettes daily in the last 30 days or used an e-cigarette on an average of 29.7 (SD 1.5) of the past 30 days. Mean cytisinicline treatment duration was 301.8 days (SD 109.2). Participants took a mean of 92.1% (SD 14.8) of expected cytisinicline doses. Overall, 315 (66.3%) patients reported at least one TEAE, most commonly abnormal dreams (8.4% of patients), insomnia (8.4% of patients), and upper respiratory tract infection (6.7% of patients). Most TEAEs (94.8%) were mild or moderate in intensity. TEAEs considered to be related to study treatment were reported by 142 (29.9%) patients. TEAEs leading to study discontinuation were reported by 27 (5.7%) patients.

Conclusions

Cytisinicline administration (3 mg TID) for up to 52 weeks was well tolerated by adult smokers and e-cigarette users who were attempting to quit. Adherence to treatment was high, and few participants with a TEAE discontinued the study. Together with previous studies demonstrating cytisinicline’s efficacy, these findings support the potential value of cytisinicline as a treatment for cigarette smoking/e-cigarette vaping cessation.

This abstract is funded by: Achieve Life Sciences