Achieve Life Sciences has announced that its ongoing ORCA-OL clinical trial evaluating the long-term safety exposure of cytisinicline has reached a critical milestone. The trial has successfully enrolled at least 300 participants who have completed six months of cumulative treatment with cytisinicline, satisfying a key requirement for the New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA). This achievement keeps the company on track for its planned NDA submission in the second quarter of 2025.
ORCA-OL Trial Details
The ORCA-OL trial is an open-label study designed to assess the long-term safety of a 3 mg cytisinicline treatment regimen, administered three times daily, in adults aged 18 years and older who are motivated to quit smoking or vaping. Conducted across 29 clinical sites in the United States, the trial aims to provide the FDA with comprehensive safety data to support the potential approval of cytisinicline. In addition to the six-month data, one-year cumulative exposure safety data from at least 100 subjects will be submitted before potential product approval.
The FDA had requested six-month safety exposure data from at least 300 participants treated with cytisinicline to be included in the company’s planned NDA, with one-year cumulative exposure safety data from a minimum of 100 participants treated with cytisinicline submitted during the NDA review period, prior to potential NDA approval.
Safety Profile and DSMC Review
The Data Safety Monitoring Committee (DSMC) conducted its second independent review of the ORCA-OL trial and reported no unexpected treatment-related adverse events. The DSMC also noted excellent adherence to the cytisinicline medication among participants. The overall safety data is consistent with previous findings from Phase 2 and Phase 3 trials, reinforcing confidence in the safety profile of cytisinicline. The DSMC has recommended that the study continue without any modifications.
Management Commentary
"Achieving this critical milestone for the NDA submission clearly advances our mission to bring treatment to people who struggle with nicotine dependence," stated Cindy Jacobs, Ph.D., M.D., President and Chief Medical Officer of Achieve. Rick Stewart, Chief Executive Officer of Achieve, added, "The completion of the cumulative six-month treatment reflects the dedication of our team and study participants, bringing us closer to our goal of potentially becoming the first new FDA-approved smoking cessation treatment in nearly two decades."
Cytisinicline: A Potential New Treatment for Nicotine Dependence
Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is currently under investigation and has not been approved by the FDA for any indication in the United States.
The Need for New Cessation Therapies
Approximately 29 million adults in the United States smoke combustible cigarettes, and over 11 million adults use e-cigarettes. Tobacco use remains the leading cause of preventable death, responsible for nearly half a million deaths in the U.S. annually. Despite available treatments, there remains a significant unmet need for more effective and accessible cessation therapies, particularly for e-cigarette or vaping cessation, where no FDA-approved treatments currently exist. Cytisinicline has been granted Breakthrough Therapy designation by the FDA to address this critical gap.
Achieve's Broader Clinical Program
To date, Achieve has successfully completed two Phase 3 clinical trials of cytisinicline in more than 1,600 subjects who either smoke cigarettes or vape nicotine e-cigarettes and have the desire to quit. Achieve has also conducted a successful end-of-Phase 2 meeting with the FDA for the vaping indication and expects to initiate its single Phase 3 clinical study in vaping later in 2025.
