Cytisinicline

In 2022, 11.6% of U.S. adults, approximately 28.8 million people, reported current cigarette smoking. CDC attributes more than 480,000 U.S. deaths annually to smoking and secondhand smoke and reports that more than 16 million Americans live with a smoking-related disease. Estimated U.S. smoking-related costs exceeded $600 billion in 2018.

ORCA-2 randomized 810 participants and ORCA-3 randomized 792 participants. With 12 weeks of cytisinicline, continuous abstinence during weeks 9–12 was 32.6% versus 7.0% with placebo in ORCA-2 and 30.3% versus 9.4% in ORCA-3. During weeks 9–24, the corresponding rates were 21.1% versus 4.8% and 20.5% versus 4.2%. Both trials provided behavioral support and reported no treatment-related serious adverse events.

ICER modeled a five-year U.S. budget impact using a hypothetical $5,000 price for a 12-week course. At that price, 4.3% of the eligible population could be treated without exceeding its $880 million annual budget-impact threshold. The manufacturer had not announced a U.S. price.

Two placebo-controlled phase 3 trials demonstrated higher smoking-abstinence rates with cytisinicline plus behavioral support than with placebo plus behavioral support. The sponsor reported an FDA complete response letter citing manufacturing deficiencies and unfinished product labeling, without efficacy or clinical safety deficiencies, and anticipated potential approval in the first half of 2027. This remains an anticipated regulatory outcome, not an approval. Economic findings depend on an unannounced U.S. price.