Obefazimod: A First-in-class Drug for the Treatment of Ulcerative Colitis

J Crohns Colitis. 2023 Nov 8;17(10):1689-1697. doi: 10.1093/ecco-jcc/jjad067.

Abstract

Biologic agents and oral small molecules are the mainstays of inflammatory bowel disease [IBD] management. However, an unmet clinical need remains for additional agents with novel mechanism of action which are effective, safe, and disease-modifying; this is due to the substantial proportion of patients who do not respond, lose response, or develop intolerance to currently marketed products. microRNAs [miRNAs] that play a role in the modulation of signal transduction pathways implicated in the development of IBD hold the potential to be used as therapeutic targets. Recently, a novel first-in-class compound, obefazimod, originally conceived as a human immunodeficiency virus [HIV] infection drug, has shown great promise in phase II induction trials for ulcerative colitis [UC] patients. Findings from the maintenance phases of trials showed that long-term obefazimod treatment provides continued improvement in clinical symptoms of disease, with a substantial proportion of patients in clinical remission, and an overall good safety profile. With a novel mechanism of action, obefazimod is an orally available small molecule with anti-inflammatory properties through the specific and selective upregulation of miR-124 expression. The aim of this paper is to critically review the available evidence related to pharmacokinetics and pharmacodynamics, and to discuss the potential clinical implications of this first-in-class oral small molecule.

Keywords: ABX464; Oral small molecules; miRNAs; obefazimod; ulcerative colitis.

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Colitis, Ulcerative* / drug therapy
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy

Substances

  • Anti-Inflammatory Agents