Eluxadoline eases IBS with diarrhea in adults

Last Updated: 2016-01-25

By Reuters Staff

NEW YORK (Reuters Health) - Eluxadoline (Viberzi, Allergan), a new oral medication with mixed opioid effects, eased symptoms of irritable bowel syndrome (IBS) with diarrhea in two phase III trials in the U.S., Canada, and the UK.

Based on those trials, eluxadoline, a peripherally acting mu receptor agonist, delta receptor antagonist, and kappa receptor agonist, was approved in May 2015 for treating IBS with diarrhea in adults.

Based on non-clinical studies, eluxadoline is thought to reduce "visceral activity without completely disrupting intestinal motility," according to a report of the trials by Dr. Anthony J. Lembo of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and colleagues online January 21 in The New England Journal of Medicine.

Between 2012 and 2014, the researchers randomly assigned a total of 2,427 patients ages 18 to 80 to receive 75-mg or 100-mg eluxadoline or placebo twice daily - either for 52 weeks in the IBS-3001 trial or for 26 weeks in the IBS-3002 trial.

In the longer trial, the second 26 weeks were used for safety assessment only.

In both trials, the primary composite outcome measure was improvement in abdominal pain and improvement in stool consistency on the same day for at least half the days of weeks 1-12 (the U.S. Food and Drug Administration endpoint) and 1-26 (the European Medicines Agency endpoint).

In IBS-3001, at week 12, this goal was achieved by 17.1% taking placebo, 23.9% taking 75-mg (p=0.01), and 25.1% taking 100-mg (p=0.004). In IBS-3002 at 12 weeks, those rates were 16.2% with placebo, 28.9% with 75 mg and 29.6% with 100 mg (p<0.001 both doses).

At week 26, primary outcome rates with placebo, 75 mg, and 100 mg, respectively, were 19.0%, 23.4% (p=0.11), and 29.3% (p<0.001) in IBS-3001 and 20.2%, 30.4% (p=0.001), and 32.7% (p<0.001) in IBS-3002.

The most common adverse events were nausea (8.1% with 75 mg, 7.5% with 100 mg, and 5.1% with placebo), constipation (7.4%, 8.6%, and 2.5%, respectively), and abdominal pain (5.8%, 7.2%, and 4.1%, respectively). Five patients in the drug groups developed pancreatitis.

"More patients who received eluxadoline than who received placebo reported significant improvement in the primary outcome measure over both intervals assessed," the researchers wrote. "Patients who received eluxadoline reported a decrease in stool frequency and in urgency, which are two of the most bothersome symptoms of IBS with diarrhea."

According to the FDA news release (http://1.usa.gov/20jtQOc), "Viberzi should not be used in patients with a history of bile duct obstruction, pancreatitis, severe liver impairment, or severe constipation, and in patients who drink more than three alcoholic beverages per day."

Dr. Lembo did not respond to requests for comment.

Furiex Pharmaceuticals, an affiliate of Allergan, funded the study and employed seven of the authors.

SOURCE: http://bit.ly/1SzudTm

N Engl J Med 2016.