Obefazimod: A First-in-class Drug for the Treatment of Ulcerative Colitis.
Séverine VermeireVirginia SolitanoLaurent Peyrin-BirouletHerbert TilgSilvio DaneseHartmut EhrlichDidier ScherrerPaul GinesteLaurence d'AgayBruce E SandsPublished in: Journal of Crohn's & colitis (2023)
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.
Keyphrases
- ulcerative colitis
- small molecule
- human immunodeficiency virus
- end stage renal disease
- chronic kidney disease
- poor prognosis
- phase ii
- newly diagnosed
- prognostic factors
- ejection fraction
- emergency department
- peritoneal dialysis
- hepatitis c virus
- rheumatoid arthritis
- antiretroviral therapy
- cell proliferation
- protein protein
- machine learning
- long non coding rna
- physical activity
- patient reported outcomes
- open label
- systemic lupus erythematosus
- climate change
- long noncoding rna
- human health
- replacement therapy
- combination therapy
- double blind
- big data