Obefazimod phase 2bUC · Induction and maintenance
ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension
Vermeire S, et al.
Lancet Gastroenterol Hepatol 2022 · PMID 36075249 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(22)00233-3 (full paper, opens in a new tab)
| Arm | Change in modified Mayo score, LS mean (95% CI) | P vs placebo | Headache |
|---|---|---|---|
| Obefazimod 100 mg | −2.9 (−3.4 to −2.5) | P=0.0039 | 27/64 (42%) |
| Obefazimod 50 mg | −3.2 (−3.7 to −2.7) | P=0.0003 | 19/63 (30%) |
| Obefazimod 25 mg | −3.1 (−3.6 to −2.6) | P=0.0010 | 13/62 (21%) |
| Placebo | −1.9 (−2.4 to −1.5) | — | 5/64 (8%) |
Efficacy was similar across the three doses, but headache rose with dose.
Source: Vermeire 2022, abstract. Efficacy in the full analysis set (two 25 mg patients excluded); headache in the safety population.
Structured abstract
BackgroundMost advanced UC therapies target cytokines, integrins, JAK signalling or S1P receptors. Obefazimod is an oral small molecule that increases microRNA-124 in immune cells, a mechanism unlike any approved IBD drug.
MethodsPhase 2b, double-blind, randomised (1:1:1:1), placebo-controlled 8-week induction trial (95 centres, 16 countries) with an open-label extension. 254 patients. Primary endpoint: Change from baseline in modified Mayo score at week 8.
ResultsPrimary result. Least-squares mean change −2.9 (100 mg), −3.2 (50 mg) and −3.1 (25 mg) vs −1.9 (placebo); P=0.0039, P=0.0003 and P=0.0010 vs placebo
Take-homeObefazimod is a first-in-class oral drug with a new mechanism that improved UC activity in phase 2b; its place will depend on the phase 3 ABTECT results once they are published.
| Patients | 254 |
|---|---|
| Population | Adults aged 18–75 with moderately to severely active UC (modified Mayo score ≥5) and documented non-response or intolerance to previous treatment; randomisation stratified by previous biologic or JAK inhibitor exposure |
| Comparison | Obefazimod 100 mg, 50 mg or 25 mg once daily by mouth vs placebo |
| Drugs | obefazimod |
| Classes | miR-124 enhancer |
| Published | Vermeire S, et al. Lancet Gastroenterol Hepatol 2022;7:1024–35. |
Key points
- All three doses improved the modified Mayo score more than placebo.
- Headache was the most common adverse event and was dose-related: 42% (100 mg), 30% (50 mg) and 21% (25 mg) vs 8% (placebo).
- Obefazimod is an oral small molecule that increases microRNA-124 in immune cells, a mechanism unlike any approved IBD drug.
- 96-week open-label maintenance (50 mg daily, 217 patients): clinical remission 54.8% at week 48 and 52.5% at week 96 by non-responder imputation (PMID 40417999).
Limitations
- The primary endpoint was a change in score, not remission.
- Short (8-week) controlled phase; the extension was open-label and uncontrolled.
- Dose-related headache.
Commentary
Context. Obefazimod is an oral UC drug whose mechanism is neither JAK inhibition nor S1P receptor modulation. All three doses beat placebo here, but the more frequent headache at 100 mg is one reason dose choice matters.
Status (October 2026). The phase 3 induction trials (ABTECT-1 and ABTECT-2) and the ABTECT maintenance trial have been presented at meetings and announced by the manufacturer, but full peer-reviewed results were not yet published, so they are not summarised here. Obefazimod is not approved in Canada.
Journal club
Design
Phase 2b, double-blind, randomised (1:1:1:1), placebo-controlled 8-week induction trial (95 centres, 16 countries) with an open-label extension. 254 patients.
Primary result. Least-squares mean change −2.9 (100 mg), −3.2 (50 mg) and −3.1 (25 mg) vs −1.9 (placebo); P=0.0039, P=0.0003 and P=0.0010 vs placebo
Validity and applicability
- The primary endpoint was a change in score, not remission.
- Short (8-week) controlled phase; the extension was open-label and uncontrolled.
- Dose-related headache.
Where it sits now
Obefazimod is a first-in-class oral drug with a new mechanism that improved UC activity in phase 2b; its place will depend on the phase 3 ABTECT results once they are published.
- ASTRO (2026): Guselkumab can be started with subcutaneous 400 mg injections instead of IV infusions, with clear benefit over placebo by week 12.
- RELIEVE UCCD (UC) (2026): Duvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.
- QUASAR (2025): Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
- TUSCANY-2 (2025): Afimkibart missed its phase 2b primary endpoint (total Mayo remission), although remission by the modified Mayo score favoured it; anti-TL1A therapy still needs phase 3 proof.
Questions for discussion
- The primary endpoint was a mean change in score, not remission. What does a mean change tell you that a responder rate does not, and vice versa?
- Efficacy looked similar across doses while headache rose with dose. How should that guide dose selection for phase 3?
- The extension was open-label and uncontrolled. How much weight would you give its remission rates?