General Information

Viberzi (eluxadoline) is a mu-opioid receptor agonist and delta-opioid receptor antagonist. In vivo studies indicate that the activity of eluxadoline at the two different opioid receptors controls GI function as well as decreases pain and potentially mitigates the constipating effect of unopposed mu agonism.

Viberzi is specifically indicated in adults for the treatment of irritable bowel syndrome with diarrhea.

Viberzi is supplied as a tablet for oral administration. The recommended dose is 100 mg taken orally twice daily with food. In patients who do not have a gallbladde, are unable to tolerate the 100 mg dose of Viberzi, are receiving concomitant OATP1B1 inhibitors or have mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, the recommended dose is 75 mg taken orally twice daily with food.

Mechanism of Action

Eluxadoline is a mu-opioid receptor agonist; eluxadoline is also a delta opioid receptor antagonist and a kappa opioid receptor agonist. The binding affinities (Ki) of eluxadoline for the human mu and delta opioid receptors are 1.8 nM and 430 nM, respectively. The binding affinity (Ki) of eluxadoline for the human kappa opioid receptor has not been determined; however, the Ki for guinea pig cerebellum kappa opioid receptor is 55 nM. In animals, eluxadoline interacts with opioid receptors in the gut.

Clinical Trial Results

The FDA approval of Viberzi was based on two randomized, multi-center, multi-national, double-blind, placebo-controlled trials (Studies 1 and 2). A total of 1,281 patients in Study 1 and 1,145 patients in Study 2 received treatment with Viberzi 75 mg, Viberzi 100 mg or placebo twice daily. All patients met Rome III criteria for IBS-D and were required to meet both of the following criteria: an average of worst abdominal pain scores in the past 24 hours of >3.0 on a 0 to 10 scale over the week prior to randomization and an average daily stool consistency score (Bristol Stool Scale or BSS) of ≥5.5 and at least 5 days with a BSS score ≥5 on a 1 to 7 scale over the week prior to randomization. Study 1 and Study 2 included identical 26-week double-blind, placebo-controlled treatment periods. Study 1 continued double-blinded for an additional 26 weeks for long-term safety (total of 52 weeks of treatment), followed by a 2-week follow-up. Study 2 included a 4-week singleblinded, placebo-withdrawal period upon completion of the 26-week treatment period. Efficacy of Viberzi was assessed in both trials using an overall composite responder primary endpoint. The primary endpoint was defined by the simultaneous improvement in the daily worst abdominal pain score by ≥30% as compared to the baseline weekly average AND a reduction in the BSS to <5 on at least 50% of the days within a 12-week time interval. In both trials, the proportion of patients who were composite responders to Viberzi was statistically significantly higher than placebo for both doses.