Achieve Life Sciences (Nasdaq: ACHV) has announced a significant step forward in the development of cytisinicline as a potential first-in-class treatment for vaping cessation. Following a successful End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), the company has secured agreement on its proposed Phase 3 study design. This milestone reinforces the potential for cytisinicline to address the critical unmet need among the growing population of e-cigarette users seeking to quit.
The FDA has agreed that one well-controlled Phase 3 trial (ORCA-V2), in conjunction with Achieve's completed Phase 2 ORCA-V1 trial, would be acceptable for a vaping cessation indication via a supplemental new drug application (sNDA). This decision streamlines the regulatory pathway for cytisinicline, potentially accelerating its availability to patients.
Phase 3 Trial Design
The planned Phase 3 ORCA-V2 trial will evaluate the efficacy and safety of 3 mg cytisinicline, administered three times daily (TID) for 12 weeks, compared to placebo. The study will enroll approximately 800 adults who use e-cigarettes or nicotine vapes and do not currently smoke cigarettes. All participants will receive behavioral support for nicotine cessation throughout the 24-week trial duration.
Key elements of the ORCA-V2 trial design include:
- Study Population: Adults aged 18 years or older who are dependent on nicotine e-cigarettes and have experienced at least one failed attempt to quit vaping.
- Primary Objective: Weekly vaping abstinence with biochemical confirmation during weeks 9 to 12 of treatment, mirroring the Phase 2 ORCA-V1 trial objective.
- Secondary Objective: Continuous vaping cessation from weeks 9 to 24.
The trial is targeted to begin in the third quarter of 2025.
Addressing an Unmet Need
There are approximately 11 million adults in the United States who use e-cigarettes, with a significant portion being young adults aged 18 to 24 who have never smoked traditional cigarettes. Notably, around 60% of vape users express a desire to quit, yet there is currently no FDA-approved treatment specifically indicated for nicotine e-cigarette cessation. Cytisinicline has been granted Breakthrough Therapy designation by the FDA to address this critical gap.
"The success of our End-of-Phase 2 meeting reaffirms the clinical development strategy for cytisinicline and its potential as a groundbreaking therapy for nicotine dependence," stated Cindy Jacobs, M.D., Ph.D., President and Chief Medical Officer of Achieve. "We are steadfast on addressing the critical unmet need in vaping cessation and pioneering a path toward the first approved treatment for this growing public health challenge."
Cytisinicline's Mechanism of Action
Cytisinicline is a plant-based alkaloid that exhibits a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction by interacting with nicotine receptors in the brain, thereby reducing the severity of craving symptoms and diminishing the reward and satisfaction associated with nicotine products. Achieve has successfully completed two Phase 3 clinical trials of cytisinicline in more than 1,600 subjects who smoke combustible cigarettes, as well as one Phase 2 clinical trial for adults who vape nicotine e-cigarettes and desire to quit.
