Introduction
Obefazimod (Obe) is an oral, once-daily (QD), small molecule that enhances the expression of microRNA-124, thereby restoring mucosal immune balance through regulation of Th17 cells and macrophages. Obe has shown efficacy in patients (pts) with moderately to severely active ulcerative colitis (UC) in two Phase 2 induction trials and subsequent open-label maintenance studies [1-3], as well as in the Phase 3 ABTECT-1 and ABTECT-2 induction trials [4].
Aims & Methods
Pts with UC in the phase 2 trials who received Obe 50mg QD (Obe-50) and achieved endoscopic improvement (Mayo Endoscopic subscore = 0 or 1), were eligible to enroll in an open label study in which they received Obe 25mg QD (Obe-25) for up to an additional 78 months. This interim analysis (cut-off date: January 5, 2026) reports efficacy outcomes (clinical remission, endoscopic improvement, endoscopic remission, and symptomatic remission – See Table 1) in pts from baseline through the Week 144 (W144) visit, using both a non-responder imputation and as observed analysis. Treatment emergent adverse events (TEAEs), serious TEAEs and study discontinuation rates were examined.
Results
Pts with UC received Obe-50 for approximately four years in the Phase 2a open-label maintenance (OLM) study and for approximately two years in the Phase 2b OLM study. Out of 174 pts who completed these studies (10 in Phase 2a OLM, 164 in Phase 2b OLM), 138 were eligible. Overall, 130 pts received treatment in the Obe-25 OLM. Among this cohort, 16 pts (12%) discontinued prior to W48, including 4 who were subsequently found to be ineligible; 7 pts (5%) discontinued between W48 and W96; and 3 pts (2%) discontinued between W96 and W144. As of the cut-off date, 113 pts (87%) completed the W48 visit, 107 (82%) the W96 visit and 104 (80%) the W144 visit. Following dose de-escalation, rates of clinical remission were 73% at W48, 69% at W96 and 68% at W144, while symptomatic remission rates ranged from 72% to 79% (NRI analysis). In the as-observed analysis, clinical remission rates were 84-85% through W144, while symptomatic remission rates ranged from 88% to 91%. Consistent trends were observed across other efficacy endpoints (Table 1). Median fecal calprotectin (FCP) ranged from 48 to 98 µg/g over the 144-week study period; among pts with available FCP data at W144, 81% (72/89) had FCP levels <250 µg/g and 69% (61/89) had levels <150 µg/g. No new safety signals were identified over the 144-week period.
Table: Efficacy at baseline, weeks 48, 96 and 144 - NRI and as observed analyses
| | Baseline
(N = 130) | Week 48
(N1 = 113) | Week 96
(N1 = 107) | Week 144
(N1 = 104) |
| Endpoints, % (n) | NRIa | As observedb | NRIa | As observedb | NRIa | As observedb |
| Clinical remission | 89.2 (116) | 73.1 (95) | 84.1 (95) | 69.2 (90) | 84.1 (90) | 67.7 (88) | 84.6 (88) |
| Symptomatic remission | 91.5 (119) | 79.2 (103) | 91.2 (103) | 72.3 (94) | 87.9 (94) | 72.3 (94) | 90.4 (94) |
| Endoscopic improvement | 96.9 (126*) | 79.2 (103) | 91.2 (103) | 76.2 (99) | 92.5 (99) | 73.8 (96) | 92.3 (96) |
| Endoscopic remission | 64.6 (84) | 56.9 (74) | 65.5 (74) | 58.5 (76) | 71.0 (76) | 57.7 (75) | 72.1 (75) |
| Clinical remission: stool frequency sub-score (SFS) ≤1, rectal bleeding sub-score (RBS) = 0 and endoscopic sub-score ≤1; symptomatic remission: SFS≤1 and RBS=0; endoscopic improvement: endoscopic sub-score ≤1; endoscopic remission: endoscopic sub-score = 0; N = number of subjects with at least one of the binary efficacy outcome assessed; N1 = number of subjects still in the trial at each timepoint. *: Four subjects were enrolled despite not meeting baseline endoscopic improvement criteria and therefore were discontinued early. a: % NRI = n/N; b: % as observed = n/N1 |
Conclusion
After 2-4 years of open-label treatment with Obe-50, a high proportion of pts maintained clinical and symptomatic remission on Obe-25 for up to three additional years. No increased incidence of infections or malignancies and no new safety signals were observed over up to seven years of treatment, supporting a favorable long-term benefit-risk profile and the understanding of the mechanism of action restoring mucosal immune balance without broad immune suppression.
References
- Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697
- Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035
- Vermeire S, et al. J Crohns Colitis. 2025; 19 : jjaf074
- Sands BE, et al. UEG Journal, 2025; 13: 1818-1820
Disclosure
BES: Abbvie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, BMS, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Fzata, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Kaleido, Kallyope, Lilly, Merck, Microba, Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, OSE Immunotherapeutics, Janssen, Palisade Bio, Pfizer, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Therapeutics, Spyre Therapeutics, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Trex Bio, Union Therapeutics, Ventyx Biosciences; SV: AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, Zealand Pharma; SD: AbbVie, Ferring, Hospira, J&J, Merck, MSD, Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim; LPB: Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia; HT: Abbvie, Abivax, Dr Falk Pharma, Ferring, Galapagos, Microbiotica, MSD, Pfizer, Takeda ; US: AbbVie, Abivax, Amgen, Galapagos, Janssen, Lilly ; DR: Abbvie, Abivax, Altrubio, Athos Therapeutics, BMS, Celltrion, Connect BioPharma, Eli Lilly, Genentech, Iterative Health, Janssen, J&J, Merck, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda, Vedanta Biosciences, Ventyx ; PSD : Abbvie, Abivax, Adiso, Alimentiv, BMS, Celltrion, Genentech, Geneoscopy, Janssen, Pfizer, Takeda ; MD : Abbvie, Abivax, Arena, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hoffmann-La-Roche, Genentech, Gilead, Janssen, Merck, Pfizer, Prometheus Biosciences, Takeda; BS: AbbVie, AltruBio, Abivax, Boehringer Ingelheim, BMS, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Landos, Materia Prima, PredictImmune, Pfizer, and Takeda; TH: Mitsubishi Tanabe Pharma Corporation, EA pharma Co., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer, Eli Lilly, Gilead Sciences, BMS, Abivax ; RA : AbbVie, Abivax, AstraZeneca, BMS, Celltrion Healthcare, Galapagos, J&J, Lilly, MSD, Pfizer, Takeda; AA: AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, BMS, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma; GDH : Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, J&J, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx; BV : Abbvie, Agomab, Alfasigma, Biogen, BMS, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, J&J, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, BMS, Domain Therapeutics, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Viatris
