In Nicotine dependence and smoking cessation, a paper available in the National Library of Medicine, co-authors shared that tobacco use is the single most preventable cause of death, disability and disease in the world and was projected to be the leading cause of death and disability across all developed and developing countries by 20201. In July 2023, the World Health Organization said that the ‘tobacco epidemic’ is one of the biggest public health threats the world has ever faced, killing over eight million people a year around the world2.
Achieve Life Sciences is a specialty pharmaceutical company committed to addressing the global smoking health and nicotine addiction epidemic through the development and commercialisation of cytisinicline. As such, the company has achieved some key milestones this year. DDW’s Megan Thomas catches up with Achieve CEO John Bencich to learn more about these milestones.
MT: Can you provide a summary of Achieve’s 2023 milestones?
JB: In April, the company reported positive topline results from its Phase II ORCA-V1 trial, which evaluated the efficacy and safety of 3mg cytisinicline dosed three times daily for 12 weeks compared to placebo in 160 adults who use e-cigarettes or nicotine vapes and who do not currently smoke cigarettes.
In May, more positive topline results were released from the Phase III ORCA-3 trial of cytisinicline. Consistent with the previously reported Phase III ORCA-2 study, ORCA-3 showed a statistically significant benefit in helping people to quit smoking compared to placebo, with low rates of adverse events.
MT: What do these results mean for escalating levels of vaping?
JB: Nicotine dependency continues to be a prominent health issue worldwide. The number of people using e-cigarettes continues to climb, as the World Health Organization reported that 41 million adults used e-cigarettes globally in 2018. Many people are turning to vaping to attempt to quit smoking, yet many are unsuccessful and become dual users of both combustibles and e-cigarettes. Evident by the rapid enrollment in our clinical trial and survey findings of people who use e-cigarettes, many people want to quit and have difficulty in doing so successfully.
MT: Why is it necessary for medical interventions to address vaping and associated problems?
JB: Nicotine, in all forms, is very addictive, and many people struggle to quit without the use of medical and/or behavioral intervention. Research in this emerging area is limited, and there are currently no treatments that are specifically approved by the FDA for e-cigarette cessation. Based on our vaping cessation trial, ORCA-V1, participants who were treated with cytisinicline were 2.6 times more likely to quit vaping compared to those who received placebo. These results are compelling and provide evidence that cytisinicline should be studied in a larger population of people who want to quit vaping, as it may increase their ability to do so successfully.
MT: These new results build on the company’s strong body of evidence demonstrating that cytisinicline has been shown in clinical trials to be a safe and effective treatment for nicotine dependence. What comes next for Achieve?
JB: The successful results from our second, confirmatory Phase III trial set the stage for the future of Achieve. We are planning on an NDA filing in the first half of 2024, and with FDA approval, cytisinicline could be the first approved treatment option for smoking cessation in almost 20 years.
MT: What wider societal impact, in terms of diseases like cancer for instance, will the successful roll out of this drug have?
The FDA approval of cytisinicline would allow people who are motivated to quit access to a new cessation treatment, thus having the potential to help with cancer prevention strategies. Smoking is a well-known contributor to many different types of diseases and accounts for 20% of all cancers. It also increases the risk of coronary heart disease and stroke by two to four times. Quitting smoking is one of the most important actions people can take to improve their health regardless of their age or years spent smoking. Quitting can lower the risk of 12 types of cancer. The ability to offer a new treatment is likely to increase the number of people who have successful quit attempts, which will transform the health industry by reducing the resource utilisation, personnel burden, and cost associated with smoking-related diseases, preventing tobacco-related deaths, improving public health, and enhancing quality of life.
MT: What are the obstacles the company faced up until this stage, and how were they overcome?
JB: Achieve is a small biotech company with only 22 full-time employees, so executing a clinical development program on this scale with limited financial and human resources has proven to be a challenge. We are grateful for the non-dilutive financing we received in a grant from the National Institutes of Health and the National Institute on Drug Abuse to offset clinical development costs in part and help us to continue our research efforts.
MT: What are the challenges and opportunities for the future?
JB: The greatest opportunity ahead is submitting our NDA and receiving FDA approval in the US, which will enhance our ability to expand access to cytisinicline globally. We believe the clinical risk is behind us, and now we hope to find a commercialisation partner who will provide the greatest opportunity for cytisinicline to make a significant public health impact globally.
MT: How will this drug differ from other options for smoking cessation and nicotine dependence?
JB: There are generally two types of pharmacologic treatments for smoking cessation, nicotine replacement and drugs like bupropion or varenicline, that work in the brain to help reduce cravings and withdrawals that occur when people stop using nicotine. Unfortunately, the non-nicotine products have had a history of troubling side effects and neuropsychiatric adverse events that have discouraged compliance and adoption. Cytisinicline is unique, in that, in our clinical trials to date, it has been exceptionally well tolerated and efficacious. We believe this will be encouraging to those who have been reluctant to try medications in the past due to side effects and to those who continue to struggle to break their nicotine dependence.