P0694 Pooled analysis of efficacy and safety of once-daily oral obefazimod in North American patients from the ABTECT Phase 3, double-blind, placebo-controlled induction 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. Here, we present a pooled analysis of the efficacy and safety of Obe in the North American (NA) subgroup of pts enrolled in the ABTECT induction trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (MMS≥ 5, with rectal bleeding sub-score (RBS) ≥ 1 and centrally read Mayo endoscopic score ≥2) who had inadequate response, loss of response, or intolerance to at least one prior systemic therapy (corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors), with no limit on the number of prior advanced therapy inadequate responders (ATIR). 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. This post-hoc analysis focuses on the subgroup of pts recruited from study defined NA centers. Efficacy endpoints included clinical remission (per MMS), clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement. All p-values are nominal. Treatment emergent adverse events (TEAEs), serious TEAEs and dropout rates were evaluated. Results Among the 1272 pts randomized in the ABTECT trials, 122 were NA pts (116 pts from USA and 6 pts from Canada). Baseline demographics and disease characteristics were well balanced between treatment groups and generally comparable between NA pts and the overall study population. In the pooled analysis, a higher proportion of NA pts receiving Obe-25 or Obe-50 vs. PBO achieved clinical remission (Obe-25-PBO difference: 13.6%, p = 0.0218; Obe-50-PBO difference: 13.2%, p = 0.0235), clinical response, and symptomatic remission with nominal significance (Table). Headache was the most common TEAE (Obe-25: 29.2%; Obe-50: 24.2%; PBO: 5.6%). Among NA pts, no serious TEAEs occurred with Obe-25, and the rate with Obe-50 was similar to PBO (3.2% vs 8.3%, respectively). TEAE leading to study discontinuations were less frequent with Obe-25 (4.2%) and Obe-50 (6.5%) vs PBO (13.9%). No opportunistic infections or malignancies were reported. Conclusion In the ABTECT induction trials, clinically meaningful improvements in efficacy measures were observed, and Obe treatment demonstrated a favorable safety profile in NA pts, consistent with the overall study population. 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 Conflict of interest: Sands, Bruce E: Grant: Janssen 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 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 Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Panaccione, Remo: Grant: Abbvie, Janssen, Pfizer, Takeda Other: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, UCB Speaker’s Fees for: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx. Ritter, Timothy E: No conflict of interest Siddiqui, Junaid: No conflict of interest Duvall, George Aaron: No conflict of interest Dulai, Parambir: Grant: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Personal Fees: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus