Publication of an expert article in JCC on obefazimod as promising therapeutic management option for ulcerative colitis patients

The authors of the publication include major European and North American Key Opinion Leaders (KOLs) in the field of IBD, e.g. Séverine Vermeire (Belgium), Virginia Solitano (Italy and Canada), Laurent Peyrin-Biroulet (France), Herbert Tilg (Austria), Silvio Danese (Italy), and Bruce Sands (United States).

The KOLs conclude, obefazimod is a first-in-class drug with a unique mechanism of action that holds great promise in the therapeutic management of ulcerative colitis (UC) patients. The experts further expect the results from the ongoing Phase III program with obefazimod for the treatment of UC (ABTECT program) will confirm the previous outcomes and their conclusions issued in this publication.

The article analyses the results generated in preclinical studies as well as clinical trials conducted with obefazimod in ulcerative colitis, rheumatoid arthritis, Covid-19 and HIV patients. The KOL’s analysis is summarized in the following main conclusions: i.Obefazimod enhances the selective splicing of a single long non-coding RNA to generate an anti-inflammatory microRNA called miR-124. miR-124 is responsible for downregulation of key pro-inflammatory cytokines and chemokines thus exerting its inflammation dampening effects. The sustained overexpression of miR-124 might explain why obefazimod provides a high remission rate in UC patients after one and two years of continued daily dosing. In parallel, miR-124 does not only decrease mucosal inflammation, but it also promotes tissue repair. ii. Evidence from Phase II clinical trials supports the anti-inflammatory effect of obefazimod. Findings from the maintenance phases of the trials showed that the long-term treatment with the molecule provides continued improvement in clinical symptoms of the disease, with a substantial proportion of patients in clinical remission. iii. All clinical studies of obefazimod have shown a consistent and good safety profile, during the induction as well as in the subsequent maintenance trials. The most common treatment-emergent adverse events (TEAEs) were headache and nausea. Headaches occurred early during the first 10 days of treatment, were generally mild to moderate and lasted only a few days. There was no signal of serious infection or malignancies. iv. Obefazimod exerted no effect on the immune system in the absence of inflammation, therefore supporting a mechanism of action as modulator of immune cell activation during inflammation but not in its absence.

These findings provide evidence that upregulating miR-124 by obefazimod reverses the expression of several pro-inflammatory cytokines triggered during inflammation but does not blunt the immune response altogether.

1,200 patients suffering from moderate to severe UC at 600 investigator sites covering North America, Europe, Latin America and Asia Pacific will be included in the two induction trials (ABTECT-1 and ABTECT-2) followed by a single maintenance trial to confirm obefazimod’s fast onset of action and its long-term efficacy. Top-line results of the two induction trials are expected to become available by the end of 2024. The results of the single maintenance trial are expected by the end of 2025.

See; Vermeire et al.: "Obefazimod: a first-in-class drug for the treatment of ulcerative colitis", JCC, published online in May 2023 (DOI: 10.1093/ecco-jcc/jjad067.