Phase 2 ORCA-V1 trial showed treatment with cytisinicline more than doubled odds of quitting e-cigarettes compared with placebo  

Cytisinicline treatment well tolerated with no serious adverse events reported and excellent compliance to study treatment

Achieve expects to conduct an End-of-Phase 2 Meeting with the FDA later this year to discuss Phase 3 trial plans

SEATTLE and VANCOUVER, British Columbia, May  06, 2024  (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, today announced publication of the ORCA-V1 trial results in the Journal of the American Medical Association (JAMA) Internal Medicine. ORCA-V1 evaluated the efficacy and safety of 3 mg cytisinicline dosed three times daily for 12 weeks compared to placebo in 160 non-smoking adults who used e-cigarettes or nicotine vapes and wanted to quit e-cigarettes. All participants received behavioral support for vaping cessation.

As reported today, the ORCA-V1 trial demonstrated that biochemically confirmed continuous vaping abstinence during the last 4 weeks of treatment, the primary outcome measure, was significantly higher for cytisinicline treatment compared to placebo. For cytisinicline treatment compared to placebo, 31.8% versus 15.1% of participants were abstinent during weeks 9 to 12, and participants receiving cytisinicline treatment had 2.6 times higher odds, or likelihood, to have quit vaping (odds ratio (OR) 2.64 [95% CI, 1.06-7.10]; P=.04)

A consistent trend in favor of cytisinicline was found across the secondary endpoints, evaluating abstinence during and beyond end of treatment. During the 12-week study treatment, the past seven-day prevalence of vaping abstinence at each week was consistently higher in the cytisinicline group than the placebo group. Similarly, the mean biochemical cotinine levels were consistently lower in the cytisinicline group than the placebo group at each weekly visit during study treatment. Including a four-week follow-up after treatment ended, continuous abstinence from weeks 9 to 16 remained higher in the cytisinicline group than the placebo group at 23.4% versus 13.2%, respectively (OR, 2.0; [95% CI, 0.82-5.32]).

"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 Dr. Nancy Rigotti, Director, Tobacco Research and Treatment Center Massachusetts General Hospital, Professor of Medicine at Harvard Medical School, and Principal Investigator of ORCA-V1. "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."

Study drug compliance was high; 72.7% and 66.0% of participants treated with cytisinicline and placebo, respectively, took >90% of study drug doses. Cytisinicline was well tolerated and no serious adverse events were reported. Similar rates of adverse events were observed between treatment arms (50.9% in the cytisinicline arm versus 54.7% in the placebo arm). The most frequent (>5%) treatment-emergent adverse events for cytisinicline subjects were sleep disturbances, anxiety, headache, fatigue, and upper respiratory tract infection and for placebo subjects were nausea, COVID-19, headache, anxiety and upper respiratory tract infection. Higher rates of headache and nausea were reported by participants treated with placebo.

"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. "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."

The prevalence of e-cigarette use by adults in the United States continues to rise. It is estimated that 4.5% among all adults in the United States and 11% among adults aged 18-24 used e-cigarettes in 2021. While adults who switch from smoking combustible cigarettes to using nicotine e-cigarettes reduce their tobacco-related health risks, e-cigarettes products are not harmless and sustain nicotine dependence. In surveys, more than half of adults who vape nicotine plan to quit. Cytisinicline, if approved, could be the first prescription drug to help people who are ready to address their addiction to e-cigarettes. Achieve plans to conduct an End-of-Phase 2 Meeting with the FDA later this year to discuss future clinical trial requirements to pursue an indication for vaping cessation.

The research and clinical study discussed in this press release was supported in part by the National Institute on Drug Abuse of the National Institutes of Health (NIH) under Award Number 4R44DA054784-02. The content of this press release is the sole responsibility of the authors and does not necessarily represent the official views of the NIH.

About ORCA-V1
The Phase 2 ORCA-V1 trial evaluated 160 adults who used e-cigarettes on a daily basis at five clinical trial locations in the United States. ORCA-V1 participants were randomized to receive 3mg cytisinicline three times daily or placebo for 12 weeks in combination with standard cessation behavioral support. The dose and administration of cytisinicline in the ORCA-V1 study is identical to that used in the Phase 3 registrational trials for smoking cessation. ORCA-V1 was supported in part by the National Institute on Drug Abuse (NIDA) of the NIH through grant funding which was awarded in two phases totaling $2.8 million.

References
1Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483.
2World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017.
3U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014.
4Birdsey J, Cornelius M, Jamal A, et al. Tobacco Product Use Among U.S. Middle and High School Students — National Youth Tobacco Survey, 2023. MMWR Morb Mortal Wkly Rep 2023;72:1173–1182.