Achieve's anti-smoking drug beats placebo in 2nd phase 3, keeping biotech on course for FDA filing

Achieve Life Sciences’ smoking cessation drug candidate cytisinicline has hit the mark in a second phase 3 clinical trial, filling in a key gap in the evidence needed to support approval. But, amid lingering doubts about the asset’s commercial prospects, Achieve still has a sub-$200 million market cap.

The phase 3 trial, ORCA-3, randomized 792 adult smokers at 20 clinical trial sites in the U.S. to receive one of two regimens of cytisinicline or placebo plus behavioral support. Both the cytisinicline regimens, which dosed patients for six or 12 weeks, beat placebo. In the 12-week analysis, 30.3% of people on cytisinicline stopped smoking, compared to 9.4% for placebo. The six-week figures were 14.8% and 6%.

Achieve verified smoking abstinence using weekly expired carbon monoxide measurements, preventing the risk that participants would misreport their smoking. The effects were durable for some patients, with the 12-week cytisinicline regimen achieving a continuous smoking cessation rate of 20.5% from Week 9 to Week 24 of the study. The rate for the placebo group was 4.2% over the same period. Subjects smoked a median of 20 cigarettes per day at baseline and had a median smoking history of 36 years with four prior quit attempts.

Insomnia was the most commonly reported adverse event, affecting 11% and 11.9% of people in the cytisinicline cohorts, compared to 7.6% of their counterparts on placebo. Abnormal dreams, nausea and headache were the next most commonly reported adverse events. No treatment-related serious adverse events were seen and, based on data from both pivotal trials, Achieve views the drug as well tolerated. 

Talking to investors on a quarterly results conference call earlier this month, Cindy Jacobs, Ph.D., M.D., chief medical officer at Achieve, said the company still has some phase 1 studies to wrap up and a pre-NDA meeting with the FDA to schedule, putting it on track to file for approval in the first half of next year.

Shares in Achieve initially rose around 15% to $9.40 in premarket trading before dropping over 3% to $7.87 by 8:45 a.m. ET. While the company has seen its stock price triple so far this year, it still only commands a small market cap. The answer to why a biotech with positive data from two phase 3 clinical trials in a major indication is valued at less than $200 million may lie in doubts about the commercial prospects of cytisinicline.

For one thing, cytisinicline, a naturally occurring substance, is ineligible for U.S. composition of matter patents. Achieve has warned investors it “may not be able to block other third parties from launching generic versions of cytisinicline” and “there may be little to nothing” to stop third parties from selling cytisinicline as a herbal or homeopathic product.

Cytisinicline will also face competition from generic versions of Pfizer’s Chantix. Off-patent copies of the drug have come to dominate the market, with sales of Chantix falling (PDF) by 98% last year. Pfizer made $8 million from the product last year, having reeled in $398 million in 2021.