Long-Term Upregulation of miR-124 in Blood and Rectal Biopsies of Patients With Moderate-to-Severe Ulcerative Colitis Receiving Obefazimod 50mg Daily for 96 Weeks

Introduction: Obefazimod is an oral small molecule that has demonstrated long-term efficacy and safety in patients with moderate-to-severe ulcerative colitis (UC) (1,2). Obefazimod is known to modulate inflammation by upregulating a specific anti-inflammatory micro-RNA (miR-124) (3). We examined the long-term effects of obefazimod on miR-124 in blood and rectal biopsies of patients enrolled in a 96-week maintenance study. Methods: Patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) during a 16-week induction phase and, irrespective of their clinical response, could enter an open-label 96-week maintenance phase with obefazimod 50mg od. Absolute quantification (QuantaSoft Pro) of the miR-124 copy number was performed at baseline, weeks 48 and 96 by using droplet digital PCR technology on 115 whole blood samples and 240 rectal biopsy samples. An ANOVA was performed including treatment, time, the interaction between treatment and time, the baseline value as fixed factor and time as repeated effect. Results: A daily treatment with obefazimod 50 mg significantly upregulated miR-124 over time in blood and rectal tissue at weeks 48 and 96 (P< 0.001 vs. baseline). The miR-124 upregulation was observed in all patients, including those previously receiving placebo during the induction phase (Table 1). Conclusion: The 96-week efficacy of obefazimod 50mg od in patients with moderate-to-severe UC is associated with a maintained increase in miR-124 expression in blood and rectal tissue. References: 1. Vermeire S, et al, Lancet Gastroenterol Hepatol 2022, 7 (11): 1024-1035. 2. Vermeire et al, J Crohns Colitis 2023. doi: 10.1093/ecco-jcc/jjad067 3. Apolit C, et al, Clin Trans Gastroenterol 2023, 14(4): p e00560. Table 1. - Upregulated miR-124 in rectal tissue and blood of patients receiving obefazimod 50 mg during the maintenance phase Treatment during the induction phase Time Rectal tissue Blood Median fold change from baseline Median fold change from baseline Obefazimod 100 mg od W48 4.8 † 128.2 † W96 7.4 † 188.3 † Obefazimod 50 mg od W48 5.8 † 230.1 † W96 10.3 † 244.4 † Obefazimod 25 mg od W48 4.5 † 308.8 † W96 8.5 † 128.5 † Placebo W48 4.8 † 237.0 † W96 7.5 † 396.8 † †: P< 0.001 vs. baseline; each timepoint (W48 and W96) is compared to the baseline using a Dunnett adjustment.