Top

Published in:

01-08-2016 | AdisInsight Report

Obeticholic Acid: First Global Approval

Authors: A. Markham, Susan J. Keam

Published in: Drugs | Issue 12/2016

Abstract

Obeticholic acid (Ocaliva^TM) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. The drug is in preregistration for this indication in the EU. This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.

Intercept Pharmaceuticals. OCALIVA (obeticholic acid) US Prescribing Information. 2016. http://www.interconnectsupport.com/ocaliva_pi.pdf. Accessed 31 May 2016.

Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145(3):574–82.CrossRefPubMed

Dainippon Sumitomo Pharma Co L, Intercept Pharmaceuticals I. Dainippon Sumitomo Pharma and Intercept Pharmaceuticals announce agreement to develop and commercialize obeticholic acid (INT-747) for chronic liver disease [media release]. 30 Mar 2011. http://www.interceptpharma.com.

Intercept Pharmaceuticals Inc. Intercept Pharmaceuticals submits applications in the U.S. and Europe for marketing approval of obeticholic acid for the treatment of primary biliary cirrhosis [media release]. Jun 29 2015. http://ir.interceptpharma.com/releasedetail.cfm?releaseid=919926.

US Food and Drug Administration. FDA approves Ocaliva for rare, chronic liver disease [media release]. May 31 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503964.htm.

Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.CrossRefPubMed

Pellicciari R, Fiorucci S, Camaioni E, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002;45(17):3569–72.CrossRefPubMed

Albanis E, Alvarez CE, Pruzansky M, et al. INT-747, a novel FXR activator, reverses hepatic fibrosis and cirrhosis in thioacetamide-induced liver injury in rats [abstract no. 1040]. Hepatology. 2005;42(Suppl 1):605–6.

Verbeke LD, Mannaerts I, Schierwagen R, et al. Obeticholic acid, an FXR agonist, reduces hepatic fibrosis in a rat model of toxic cirrhosis [abstract no. P0445]. J Hepatol. 2015;62(Suppl 2):S479.CrossRef

10.

Nevens F, Andreone P, Mazzella G, et al. An international phase 3 study of the FXR agonist obeticholic acid in PBC patients: effects on markers of cholestasis associated with clinical outcomes and hepatocellular damage [abstract no. 295]. Hepatology. 2014;60(Suppl 4):347A–8A.

11.

Trauner MH, Nevens F, Andreone P, et al. Durable response in the markers of cholestasis through 18 months of open-label long term safety extension study of obeticholic acid in primary biliary cirrhosis [abstract no. Sa1579]. Gastroenterology. 2016;150(4 Suppl 1):S1073–4.CrossRef

12.

Hirschfield GM, Mason A, Luketic V, et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2015;148(4):751–61.CrossRefPubMed

13.

Kowdley KV, Shah H, Mason A, et al. Long-term safety and efficacy of obeticholic acid treatment in primary biliary cirrhosis after more than 4 years of treatment [abstract no. 628]. Hepatology. 2015;62(Suppl 1):521A–2A.

14.

Walters JR, Johnston IM, Nolan JD, et al. The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid. Aliment Pharmacol Ther. 2015;41(1):54–64.CrossRefPubMed

15.

Ratziu V, Sanyal AJ, MacConell L, et al. Regenerate: a phase 3, double-blind, randomized, placebo-controlled multicenter study of obeticholic acid therapy for nonalcoholic steatohepatitis [abstract no. THU-488]. J Hepatol. 2016;64(Suppl 2):S294–5.

Title: Obeticholic Acid: First Global Approval
Authors: A. Markham
Susan J. Keam
Publication date: 01-08-2016
Publisher: Springer International Publishing
Published in: Drugs / Issue 12/2016
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-016-0616-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Obeticholic Acid: First Global Approval

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2016

Unmet Needs in LDL-C Lowering: When Statins Won’t Do!

Erratum to: Olmutinib: First Global Approval

Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection

Diclofenac Sodium Bolus Injection (DylojectTM): A Review in Acute Pain Management

Atezolizumab: First Global Approval

Daptomycin Pharmacokinetics and Pharmacodynamics in Septic and Critically Ill Patients