- Research Article
- 10.1093/ecco-jcc/jjaf231.875
P0694 Pooled analysis of efficacy and safety of once-daily oral obefazimod in North American patients from the ABTECT Phase 3, double-blind, placebo-controlled induction trials
- Jan 01, 2026
- Journal of Crohn s and Colitis
- B E Sands + 10 more +10
Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has been studied in two Phase 2 induction trials and subsequent open-label maintenance studies [1-3] in patients (pts) with moderately to severely active ulcerative colitis (UC). In Phase 3 ABTECT-1 [NCT05507203] and ABTECT-2 [NCT05507216] 8-week induction trials, Obe achieved clinically meaningful improvements in clinical, endoscopic and histologic endpoints. Here, we present a pooled analysis of the efficacy and safety of Obe in the North American (NA) subgroup of pts enrolled in the ABTECT induction trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (MMS≥ 5, with rectal bleeding sub-score (RBS) ≥ 1 and centrally read Mayo endoscopic score ≥2) who had inadequate response, loss of response, or intolerance to at least one prior systemic therapy (corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors), with no limit on the number of prior advanced therapy inadequate responders (ATIR). Pts were randomized 2:1:1 to Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25) or placebo (PBO) for 8 weeks. This post-hoc analysis focuses on the subgroup of pts recruited from study defined NA centers. Efficacy endpoints included clinical remission (per MMS), clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement. All p-values are nominal. Treatment emergent adverse events (TEAEs), serious TEAEs and dropout rates were evaluated. Results Among the 1272 pts randomized in the ABTECT trials, 122 were NA pts (116 pts from USA and 6 pts from Canada). Baseline demographics and disease characteristics were well balanced between treatment groups and generally comparable between NA pts and the overall study population. In the pooled analysis, a higher proportion of NA pts receiving Obe-25 or Obe-50 vs. PBO achieved clinical remission (Obe-25-PBO difference: 13.6%, p = 0.0218; Obe-50-PBO difference: 13.2%, p = 0.0235), clinical response, and symptomatic remission with nominal significance (Table). Headache was the most common TEAE (Obe-25: 29.2%; Obe-50: 24.2%; PBO: 5.6%). Among NA pts, no serious TEAEs occurred with Obe-25, and the rate with Obe-50 was similar to PBO (3.2% vs 8.3%, respectively). TEAE leading to study discontinuations were less frequent with Obe-25 (4.2%) and Obe-50 (6.5%) vs PBO (13.9%). No opportunistic infections or malignancies were reported. Conclusion In the ABTECT induction trials, clinically meaningful improvements in efficacy measures were observed, and Obe treatment demonstrated a favorable safety profile in NA pts, consistent with the overall study population.
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