ORCA-1

ORCA-2 was designed to evaluate the efficacy and safety of 3mg cytisinicline dosed 3 times daily for a period of 6-weeks or 12-weeks compared to placebo in 810 adult smokers (randomized 1:1:1). Subjects were monitored for smoking abstinence for 24 weeks post randomization and received standard behavioral support for the duration of the trial.

Data Results

The primary endpoints for ORCA-2 were biochemically verified continuous abstinence measured during the last 4 weeks of treatment. Both the 6- and 12-week cytisinicline treatments demonstrated significantly better quit rates than placebo with odds ratios of 8.0 and 6.3, respectively.

  • Subjects who received 12 weeks of cytisinicline treatment had 6.3 times higher odds, or likelihood, to have quit smoking during the last 4 weeks of treatment compared to subjects who received placebo (p<0.0001). The abstinence rate during weeks 9-12 was 32.6% for cytisinicline compared to 7.0% for placebo.

  • Subjects who received 6 weeks of cytisinicline treatment had 8 times higher odds, or likelihood, to have quit smoking during the last 4 weeks of treatment compared to subjects who received placebo (p<0.0001). The abstinence rate during weeks 3-6 was 25.3% for cytisinicline compared to 4.4% for placebo.

Safety Profile

  • Well-tolerated with single digit rates of adverse events (AEs)

  • No treatment-related serious adverse events reported

Most commonly reported AEs (>5% Overall)

Low rates of AEs compares favorably to currently approved smoking cessation products

Design

  • Placebo-controlled & double-blind
  • 3 treatment arms: Placebo vs 6 or 12 weeks cytisinicline
  • Cytisinicline treatment for 6 or 12 weeks

    • Does longer treatment lead to better efficacy?
    • Does continued treatment prevent early relapses?
  • Primary Endpoint: 4-week continuous abstinence ON treatment
  • Follow up to 6 months
ORCA-2 Schematic