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Abstract Background Obefazimod (Obe) is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 for the treatment of moderately to severely active ulcerative colitis (UC). Patients (pts) with UC report fatigue as one of the major complaints which negatively impacts quality of life. Here we report efficacy data from two phase 3, 8-week, induction trials on patient-reported fatigue. Methods In the Phase 3 ABTECT 1 [NCT05507203] and ABTECT 2 [NCT05507216] trials, pts with UC were randomized 2:1:1 to receive Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25), or placebo QD (PBO) for 8 weeks. Pts reported fatigue in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Numerical Rating Scale (NRS). FACIT-F includes 13 items measuring fatigue and its impacts. Scores range from 52 to 0: higher scores=less fatigue. Meaningful within patient change (MWPC) and fatigue remission were defined as a change of ≥ 5 points and a score of > 40 points, respectively. Fatigue NRS was collected in a daily electronic diary. Pts rated fatigue on a scale from 0 to 10; higher scores=worse fatigue. Fatigue NRS remission was defined as a score of ≤ 2. All p-values are nominal. Results 1272 pts were randomized and treated in ABTECT-1 (n = 636) and ABTECT-2 (n = 636); 747 pts had FACIT-F and 1241 pts had Fatigue NRS data at baseline. At baseline, pts with FACIT-F data had mean scores of 25.8, 25.3, and 24.5 in the Obe-50 mg, Obe-25 mg, and PBO groups, respectively. At Week 8, Obe-treated pts reported improved fatigue on the FACIT-F scores vs PBO: mean 35.0, 35.7, and 30.0 in the Obe-50 mg, Obe-25 mg, and PBO groups, respectively (Obe-50:Δ4.7 and Obe-25:Δ5.4, both p < 0.0001). At Week 8, a greater proportion of Obe pts had a MWPC: 45.9% for Obe-50 and 50.0% for Obe-25 vs 35.2% for PBO (Obe-50:Δ11.1, p < 0.05 and Obe-25:Δ15.1, p < 0.01). At Week 8, a greater proportion of Obe patients had a remission of FACIT-F: 22.2% for Obe-50 and 28.3% for Obe-25 vs 13.4% for PBO (Obe-50:Δ9.0, p < 0.05 and Obe-25:Δ14.6, p = 0.001). At baseline, pts with Fatigue NRS data had mean scores of 6.4, 6.3 and 6.4 in the Obe-50 mg, Obe-25 mg, and PBO groups, respectively. At Week 8, Obe-treated pts reported improved Fatigue NRS scores: 4.6, 4.3, and 5.3 Obe-50 mg, Obe-25 mg, and PBO groups, respectively (Obe-50:Δ-0.8 and Obe-25:Δ-0.9, both p < 0.0001). At Week 8, a greater proportion of Obe-treated pts had a remission of fatigue: 17.1% for Obe-50 and 22.9% for Obe-25 vs 7.7 % for PBO (Obe-50:Δ9.5, p = 0.0001 and Obe-25:Δ15.2, p < 0.0001). See Table. Conclusion Pts with moderately to severely active UC treated with Obe reported marked improvement in fatigue compared to PBO across both doses in ABTECT induction trials. Conflict of interest: Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Sands, Bruce E: Grant: Janssen, Bristol Myers Squibb, Pfizer Personal Fees: Abivax SA Abbvie Adiso Therapeutics Agomab Therapeutics Alimentiv Amgen AnaptysBio AstraZeneca Biora Therapeutics Boehringer-Ingeleim Bristol Myers Squibb Celltrion, Inc. ClostraBio Cytoki Pharma EcoR1 Capital Eli Lilly and Company Enthera Equilium, Inc. Ensho Therapeutics Evommune Ferring Galapagos Genentech, Inc. Gilead Sciences GlaxoSmithKline Gossamer Bio Imhotex Immunyx Pharma Ltd. Index Pharmaceuticals Innovation Pharmaceuticals Janssen Janssen Biotech Janssen Pharmaceutica NV Janssen Research & Development, LLC Janssen Scientific Affairs, LLC Janssen-Cilag PTY, Ltd. Johnson & Johnson Kaleido Kallyope Kyowa Kirin, Inc. Merck & Co. Microba Microbiotica Limited Mirador Therapeutics Morphic Therapeutic MRM Health NV Palisade Therapeutics Pfizer, Inc. Prometheus Biosciences Prometheus Laboratories Protagonist Therapeutics, Inc. Q32 Bio Sanofi Sorriso Therapeutics Surrozen Takeda Target RWE Teva TLL Pharmaceutical Tr1x Union Therapeutics Ventyx Biosciences Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences Gregus, Milos: Patricipation in clinical studies/ company sponsored grants: Eli Lilly Slovakia, AbbVie, Celltrion, Takeda, Roche Speaker / lecturer: AbbVie, Janssen, Pfizer Expert advisor: AbbVie, Eli Lilly, Takeda, Zentiva Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, 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 Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx Seidler, Ursula: Consultant for Abivax, Amgen, Janssen speaker for Abivax, Janssen and research grants from Abbvie, Abivax, Janssen, Boehringer Ingelheim, Eli Lilly, Gilead Sciences, MSD, Roche. Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Rabbat, Chris: Employee of Abivax Fine, Jennifer T: Employee of Abivax Shan, Kejia: employee of Abivax Dolan, Chantal M: Paid Consultant for Genentech, Roche, Abivax, Regenxbio, Boerhinger Ingelhiem, Pharmacoevidence, Mcure Bio Jacobstein, Doug: Employee of Abivax Cataldi, Fabio: Employee of Abivax Siegmund, Britta: Grant: Pfizer Other: Consultant: Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Galapagos, Janssen/Johnson & Johnson, Materia Prima, MSD, Pfizer, Takeda, Wedbush Securities. Speaker: Abbvie, AlfaSigma, Bristol Myers Squibb, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, Ferring, Galapagos, Janssen/Johnson & ampJohnson, MD Education, MSD, Pfizer, Tr1xBio.
Published in: Journal of Crohn s and Colitis
Volume 20, Issue Supplement_1