Achieve Life Sciences Announces Positive Results for Simplified Cytisinicline Dosing Schedule

Achieve Life Sciences has announced positive results from the ORCA-1 dose-selection trial of cytisinicline for smoking cessation. The outcome of the 254-subject, ORCA-1 trial is the selection of 3.0 mg, three times daily (TID) for Phase 3 development.

The primary endpoint was the reduction in daily smoking, a self-reported measure. Three of the four cytisinicline treatment arms demonstrated a statistically significant improvement, as defined in the protocol as p < 0.05, compared to placebo. The fourth arm trended to significance (p= 0.052). Across all treatment arms, over the 25-day treatment period, subjects on cytisinicline experienced a 74-80% median reduction in the number of cigarettes smoked, compared to a 62% reduction in the placebo arms.

The secondary endpoint of the trial was a 4-week continuous abstinence rate, which is the relevant endpoint for regulatory approval. Cytisinicline treatment showed significant improvements in abstinence rates compared to placebo. The most impressive results were observed in the 3 mg TID treatment arm which demonstrated a 54% abstinence rate at week 4, compared to 16% for placebo (p < 0.0001) and a continuous abstinence rate, weeks 5 through 8, of 30% for cytisinicline compared to 8% for placebo (p= 0.005).

All four cytisinicline arms demonstrated statistically significant (p < 0.05) reductions in expired carbon monoxide (CO), a biochemical measure of smoking activity. Expired CO levels declined by a median of 71-80% in the cytisinicline treatment arms, compared to only 38% in the placebo arms. The lack of consistency in the reduction of expired CO levels compared to the self-reported data suggest potential under-reporting of cigarettes smoked by subjects on placebo.

"The robust efficacy results in the simplified, three times daily dosing arms exceeded our expectations, particularly, the statistically significant abstinence rates. This is of importance given that a continuous abstinence rate is the endpoint for regulatory approval in smoking cessation trials," said Rick Stewart, Chairman and CEO of Achieve. "In addition to efficacy, the cytisinicline safety data observed in ORCA-1 reflects the historically strong safety profile already experienced in Central and Eastern Europe."

Adherence to study treatment was greater than 98.5% across all arms and cytisinicline was well-tolerated with no serious adverse events reported. The most commonly reported (>5%) adverse events (AEs) across all cytisinicline treatment arms versus placebo were abnormal dreams, insomnia, upper respiratory tract infections, and nausea. In the 3 mg TID treatment arm versus placebo, the most common AEs were abnormal dreams, insomnia, and constipation (each 6% vs 2%), upper respiratory tract infections (6% vs 14%), and nausea (6% vs 10%).

The Company expects to conduct further analyses of the ORCA-1 trial and submit data for presentation at a future medical meeting. Additionally, Achieve plans to discuss the trial's outcome with the FDA and finalize Phase 3 protocol details in the second-half of 2019.

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