FDA Advisors Recommend Dropping Boxed Warning in Chantix Label

Phase 3 data show acceptable rates of neuropsychiatric events

At a joint meeting, the FDA’s Psychopharmacologic Drugs Advisory Committee and Drug Safety Risk Management Advisory Committee have reviewed data from a study that evaluated the neuropsychiatric safety of the smoking-cessation drug varenicline (Chantix, Pfizer). By a majority vote, the committees recommended removing the boxed warning regarding serious neuropsychiatric adverse events from the varenicline labeling.

Earlier this year, Pfizer submitted a supplemental new drug application to the FDA requesting updates to the varenicline labeling based on safety and efficacy outcomes from the pivotal Evaluating Adverse Events in a GLobal Smoking CEssation Study (EAGLES). In addition to requesting removal of the boxed warning, Pfizer proposed retaining the “warnings and precautions” section in the labeling regarding serious neuropsychiatric events occurring in patients attempting to quit smoking and updating that section with EAGLES data.

The EAGLES trial was a randomized, double-blind, triple-dummy, placebo-controlled and active-controlled (nicotine patch; 21 mg/day with taper) study of varenicline (1 mg twice daily) and bupropion (150 mg twice daily) for 12 weeks, with 12-week nontreatment follow-up, conducted in 16 countries between November 30, 2011, and January 13, 2015. The participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit. The study’s primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events. The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 through 12.

A total of 8,144 participants were randomly assigned to a psychiatric cohort (n = 4,116 [4,074 included in the safety analysis]) or a nonpsychiatric cohort (n = 4,028 [3,984 included in the safety analysis]). In the nonpsychiatric cohort, 13 (1.3%) of 990 participants reported moderate or severe neuropsychiatric adverse events in the varenicline group; 22 (2.2%) of 989 in the bupropion group; 25 (2.5%) of 1,006 in the nicotine patch group; and 24 (2.4%) of 999 in the placebo group. In the psychiatric cohort, moderate or severe neuropsychiatric adverse events were reported in 67 (6.5%) of 1,026 participants in the varenicline group; 68 (6.7%) of 1,017 in the bupropion group; 53 (5.2%) of 1,016 in the nicotine patch group; and 50 (4.9%) of 1,015 in the placebo group. Varenicline-treated participants achieved higher abstinence rates compared with those receiving placebo (odds ratio [OR]: 3.61), the nicotine patch (OR: 1.68), or bupropion (OR: 1.75).

The findings were published online in The Lancet in April.

Varenicline was approved by the FDA in May 2006 as a prescription medication that, along with support, helps adults 18 years of age and older stop smoking.

Sources: Pfizer; September 14, 2016; and Lancet; April 22, 2016.