DOP060 Impact of baseline disease extent on efficacy of obefazimod in patients with moderately to severely active ulcerative colitis: pooled results from ABTECT-1 and ABTECT-2 phase 3 trials

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. Disease extent is a key factor in UC that influences both disease behavior and therapeutic decision-making [4]. Here we report the influence of baseline disease extent on Obe efficacy in pts from the two ABTECT induction trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (modified Mayo score (MMS)≥ 5, with rectal bleeding sub-score (RBS) ≥ 1 and centrally read endoscopic score ≥2) who had inadequate response, loss of response, or intolerance to at least one prior therapy with no limit on the number of prior advanced therapy inadequate responses. 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. For this post-hoc analysis, pts were categorized by baseline disease extent as designated by investigator: proctosigmoiditis, left-sided colitis, or extensive colitis. Efficacy endpoints evaluated in a pooled analysis included clinical remission (per MMS) clinical response, endoscopic improvement/remission, symptomatic response/remission, and histo-endoscopic mucosal improvement (HEMI). All p-values are nominal. Results Among randomized and treated pts in ABTECT trials, 280 presented with proctosigmoiditis, 474 with left-sided colitis, and 497 with extensive colitis. In both trials, baseline demographics and disease characteristics were overall similar across treatment groups, regardless of baseline disease extent. In the pooled analysis, greater proportions of pts treated with Obe-25 and Obe-50 versus PBO achieved clinical remission in pts with proctosigmoiditis (Obe-25-PBO difference: 16.1%, p = 0.0009; Obe-50-PBO difference: 19.5%, p < 0.0001) and left-sided colitis (Obe-25-PBO difference: 21.1%, p < 0.0001; Obe-50-PBO difference: 23.6%, p < 0.0001), and met all other evaluated efficacy endpoints with nominal significance (Table). In pts with extensive colitis at baseline, greater proportions of pts treated with Obe-50 versus PBO achieved clinical response, symptomatic response/remission, endoscopic improvement, and HEMI with nominal significance. Conclusion In both ABTECT induction trials, obefazimod demonstrated consistent efficacy at W8 across all baseline disease extents including proctosigmoiditis, left-sided, and extensive colitis. References: 1.Vermeire S, et al. J Crohns Colitis. 2023;17:1689-1697 2.Vermeire S, et al. Gastroenterology 2021;160:2595-2598 3.Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022;7:1024-1035 4.Eder P, et al. Journal of Crohn’s and Colitis, 2023;17(1):1-49. Conflict of interest: Heeren, Sonja: Dr. Sonja Heeren has served as a consultant or advisory board member for Alfasigma, Amgen, MSD, Abbvie, Galapagos, Lilly, Janssen, Takeda, Shire, and Pfizer has received speaker honoraria from Abbvie,Alfasigma, AstroPharma, Galapagos, Falk,Ferring, Gilead, Janssen, Lilly, MSD, Roche, Shire, Stada, Takeda, and Vifor and has acted as a past or present Principal Investigator for studies sponsored by Abbvie, Abivax,Agomab, Alimentiv, Amgen, Boehringer, BioAnaptys, Ferring, Galapagos, Janssen, Lilly, MSD, Merck, Novartis, Roche, Pfizer, Sanofi,Shire, and Takeda. Dulai, Parambir: Grant: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Personal Fees: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Neneman, Beata: No conflict of interest Bunganič, Bohuš: No conflict of interest Pumprla, Jiri: Dr. Pumprla served as the Principal Investigator for clinical trial sponsored by Abivax which manufactures the investigational product studied in this research. Dr. Pumprla has also served as principal investigator for clinical trials sponsored by Amgen, AstraZeneca, Arena/Pfizer, Arrowhead, Bayer, BMS, Boehringer Ingelheim, Celgene, Cinclus, Eli Lilly, Esperion, Fournier, Gan-Lee, Genentech/Roche, Gilead, GSK, Janssen/JnJ, Kowa, Morphic, Mylan, New Amsterdam, Novartis, Phathom, Prometheus, Salix, Sanofi, Shire, Takeda, Topivert and Vedanta. Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Peyrin-Biroulet, Laurent: Grant: Takeda, Fresenius Kabi, Celltrion, Medac, MSD Personal Fees: 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. Other: SUPPORT TRAVEL : Abbvie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots.