Introduction
Obefazimod (Obe) is an oral, once-daily (QD), small molecule that enhances expression of microRNA-124, which restores 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 the Phase 3 8-week ABTECT-1 and ABTECT-2 induction trials (NCT05507203, NCT05507216) [1]. Here, we report the efficacy and safety results of the subsequent 44-week ABTECT-Maintenance trial (ABTECT-M, NCT05535946).
Aims & Methods
The phase 3, multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderately to severely active UC who had inadequate response to at least one prior therapy, with no upper limit on the number of prior advanced therapies. Pts were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg (Obe-50), obefazimod 25 mg (Obe-25), or placebo (PBO) for 8 weeks; those who achieved clinical response to Obe were then re-randomized into a 44-week maintenance trial to receive Obe-50, Obe-25, or PBO in a 1:1:1 ratio. The primary endpoint was clinical remission at week 44 in ABTECT-M (52 weeks overall). Treatment emergent adverse events (TEAEs), serious TEAEs and study discontinuation rates were examined.
Results
A total of 1272 pts were randomized and treated in ABTECT induction trials, of which 580 achieved clinical response to Obe induction therapy and entered ABTECT-M. At week 44 of ABTECT-M, a significantly higher proportion of pts receiving Obe-50 (51.3 %) or Obe-25 (50.8%) vs PBO (10.4%) achieved clinical remission (Obe-50-PBO difference: 40.3%, p<0.0001; Obe-25-PBO difference: 39.3%, p<0.0001) and met all key secondary endpoints (Table). The overall rate of serious adverse events and treatment emergent adverse events (TEAEs) leading to study drug discontinuation for pts treated with Obe were similar to PBO. Proportions of pts who reported at least one TEAE were 71.8%, 58.0%, and 50.0% for Obe-50, Obe-25, and PBO, respectively. No safety signal was observed for serious, severe, or opportunistic infections, malignancies, pancreatitis, or headache.
Table: 44-week efficacy of obefazimod in ABTECT-Maintenance Phase 3 study
| Efficacy Endpoints at week 44, % (n) | PBO
(N= 192) | Obe-25
(N= 193) | Obe-50
(N=195) | Between group diff.
Obe-25 vs PBO | Between group diff.
Obe-50 vs PBO |
| Clinical remission | 10.4 (20) | 50.8 (98) | 51.3 (100) | 39.3
p<0.0001 | 40.3
p<0.0001 |
| CS-free Clinical remission* | 9.9 (19) | 45.1 (87) | 47.7 (93) | 35.1
p<0.0001 | 38.0
p<0.0001 |
| Sustained Clinical remission** | 15.7 (8/51) | 67.1 (49/73) | 65.6 (40/61) | 52.8
p<0.0001 | 49.1
p<0.0001 |
| Clinical response | 26.5 (51) | 69.9 (135) | 75.4 (147) | 42.8
p<0.0001 | 49.7
p<0.0001 |
| Endoscopic improvement | 12.5 (24) | 54.9 (106) | 64.1 (125) | 42.5
p<0.0001 | 51.0
p<0.0001 |
| Endoscopic remission | 9.9 (19) | 41.5 (80) | 47.7 (93) | 31.4
p<0.0001 | 37.8
p<0.0001 |
| HEMI | 10.4 (20) | 50.3 (97) | 57.4 (112) | 39.4
p<0.0001 | 46.5
p<0.0001 |
| Symptomatic remission | 22.9 (44) | 66.8 (129) | 65.6 (128) | 42.5
p<0.0001 | 41.0
p<0.0001 |
NRI is used for subjects with missing outcome at Week 44 and subjects reporting any IE prior to Week 8; % Difference is for Obe minus placebo and is based on estimated common risk difference using the Mantel-Haenszel weights adjusting for the randomization stratification factors: clinical remission at maintenance baseline (yes/no), induction treatment (25 mg/50 mg), and maintenance baseline oral corticosteroids usage (yes/no). p-values are two sided. a: for pooled analysis, all p-values are nominal; The primary and key secondary endpoints were alpha-controlled, clinical response was not. Clinical remission: stool frequency sub-score (SFS) ≤1, rectal bleeding sub-score (RBS) = 0 and endoscopic sub-score ≤1; Clinical response: decrease from baseline in the MMS ≥ 2 points and ≥30% from baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1; Endoscopic improvement: endoscopic sub-score ≤1; HEMI: combination of histologic improvement (Geboes histologic score ≤3.1) and endoscopic improvement (endoscopy sub-score ≤1); Symptomatic remission: RBS=0, SFS <1; *CS-free clinical remission: clinical remission at Week 44 and CS-free for at least 12 weeks immediately prior to Week 44; **Sustained clinical remission: clinical remission after maintenance baseline in the sub-population of subjects in clinical remission at Week 8 of the induction study.
|
Conclusion
Among pts with moderately to severely active UC, both Obe-25 and Obe-50 resulted in higher clinical remission rates than PBO in the maintenance trial, with significant benefits across all key secondary endpoints. Obe was well-tolerated during the 52 weeks of the trial, and no new safety signals were identified.
References
1. 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.
XT : Celltrion, AbbVie, J&J, Lilly, Takeda, Alpha Sigma, Dr. Falk, Abivax, Biogen, Fresenius Kabi, MSD, Pfizer, Tillotts, and Thabor Therapeutics.
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.
FB: AbbVie, Amgen, Arena Pharmaceuticals, Celgene, Celltrion, Ferring, Fresenius Kabi, J&J, Merck Sharp & Dohme, Pfizer Inc, and Sandoz.
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
