Eluxadoline: First Global Approval

Abstract

Eluxadoline (Viberzi(™)), developed by Actavis (now Allergan), is an orally administered, first-in-class compound that functions as both a µ-opioid receptor agonist and a δ-opioid receptor antagonist, and is indicated for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D) in adults. The agent was originally developed by Janssen Pharmaceutica. Eluxadoline has been approved in the US, and submissions to other global authorities are being contemplated or planned. This article summarizes the milestones in the development of eluxadoline leading to this first approval for IBS-D.

Spotlight on eluxadoline for the treatment of patients with irritable bowel syndrome with diarrhea

“…IBS-D is commonly characterized by pain and diarrhea, and eluxadoline was developed with a view to address both these symptoms. 20 , 28 Eluxadoline is an amino acid amide with a molecular weight of 569.65 g/mol and a molecular formula of C 32 H 35 N 5 O 5 ; 5-[[[(2S)-2-amino-3-[4-(aminocarbonyl)-2,6-dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2yl)ethyl]amino]methyl]-2-methoxybenzoic acid ( Figure 1 ).…”

“… 19 , 29 – 31 It has poor oral bioavailability and is used for its local effects at opiate receptors in the gastrointestinal tract. 20 Eluxadoline is a schedule IV drug in the US, subject to control under the Federal Controlled Substances Act of 1970, in the same class with tramadol and benzodiazepines. 20 , 28 …”

“…A new drug in the treatment for patients with IBS-D is eluxadoline (Viberzi ™ , Truberzi ™ ; Allergan Ltd, Dublin, Ireland). It was approved in May 2015 by the US Food and Drug Administration (FDA) and September 2016 by the European Medicines Agency (EMA) as a new agent for IBS-D 20 and has been recommended as a possible third-line option for IBS-D by the National Institute for Health and Care Excellence (NICE), UK. 21 In the current paper, we review its efficacy and safety with methods of systematic review and meta-analysis.…”

Effect of Hepatic Impairment on Eluxadoline Pharmacokinetics

“…Clinical studies in healthy volunteers found that a single oral dose of eluxadoline was poorly absorbed, with the drug being excreted primarily through the feces and with no identifiable metabolites in the urine . Low levels of eluxadoline have also been found in the hepatic portal vein in nonclinical studies, and clinical data suggest that eluxadoline is cleared primarily by OATP1B1‐mediated hepatic uptake and subsequent biliary excretion without significant hepatic metabolism …”

“…FDA‐approved therapies for adults with IBS‐D include eluxadoline, rifaximin, and alosetron (specifically for women with severe IBS‐D) . Eluxadoline (Viberzi; Furiex Pharmaceuticals, Inc, a subsidiary of Allergan plc, Parsippany, New Jersey) is a mixed μ‐opioid receptor and κ‐opioid receptor agonist and δ‐opioid receptor antagonist that is locally active in the gastrointestinal tract . In 2 phase 3 clinical trials, eluxadoline 75 mg and 100 mg twice daily demonstrated efficacy in improving the abdominal pain and stool consistency associated with IBS‐D, measured by a composite efficacy end point combining stool consistency and abdominal pain responses .…”