{
  "abstract": "Introduction Obefazimod (Obe) is an oral, once-daily (OD), small molecule which enhances expression of microRNA-124 and has been studied in Phase 2 induction trials and open-label maintenance studies [1-3] in patients (pts) with moderately to severely active ulcerative colitis (UC). We report efficacy and safety of two Phase 3, 8-week, ABTECT induction trials in adult pts with UC.Methods The multicentre, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (MMS≥ 5, RBS ≥ 1 and centrally read endoscopic score >2) who had inadequate response, loss of response, or intolerance to at least one prior therapy. Pts were randomized 2:1:1 to Obe 50 mg OD (Obe-50), Obe 25 mg OD (Obe-25) or placebo (PBO) for 8 weeks. The primary endpoint was clinical remission (per MMS); secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.Results 1272 pts were randomized and treated in both trials; baseline demographics and disease characteristics were similar between groups; 45.3% and 49.3% of pts had inadequate response to 1 or more advanced therapies. A significantly higher proportion of pts receiving Obe-50 (ABTECT-1:21.7%, ABTECT-2: 19.8%) vs PBO (2.5-6.3%) achieved clinical remission (Obe-50-PBO, ABTECT-1: Δ 19.3%, p<0.0001; ABTECT-2: Δ 13.4%, p=0.0001) and all key secondary endpoints were met in both trials. A significantly higher proportion of pts receiving Obe-50 (17.9-18.9%) vs PBO (4.4-5.7%) achieved endoscopic remission. In ABTECT-1, a significantly higher proportion of pts receiving Obe-25 vs PBO achieved clinical remission (Obe-25-PBO, Δ 21.4%, p<0.0001) and endoscopic remission (Obe-25-PBO, Δ 23.1%, p<0.0001) and all key secondary endpoints were met. In a pooled analysis, both Obe-50 and Obe-25 met all primary and secondary endpoints with nominal significance (p<0.0001). 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 59.4%, 46.9%, and 53.2% for Obe-50, Obe-25, and PBO, respectively in ABTECT-1 and 61.0%, 50.9%, and 48.4% respectively in ABTECT-2. The most frequent TEAE was headache (Obe-50: 20.8-25.8%; Obe-25: 14.5-15.6%; PBO: 5.7%). The headaches were mild, transient, short in duration and not a barrier to treatment. No signal was observed for serious, severe, or opportunistic infections or malignancies.Conclusion In both ABTECT induction trials, obefazimod treatment led to statistically significant improvements in clinical, endoscopic, symptomatic and combined endoscopic-histologic endpoints at week 8. Obe was well tolerated with no new safety signals identified.",
  "authors": [
    {
      "affiliations": [
        "Addenbrooke’s Hospital, Cambridge, UK"
      ],
      "name": "Timothy Raine"
    },
    {
      "affiliations": [
        "Northern Care Alliance NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Jimmy K Limdi"
    },
    {
      "affiliations": [
        "Guy’s & St Thomas’ Hospital, London, UK"
      ],
      "name": "Mark Samaan"
    },
    {
      "affiliations": [
        "King’s College Hospital, London, UK"
      ],
      "name": "Alexandra Kent"
    },
    {
      "affiliations": [
        "Royal London Hospital, London, UK"
      ],
      "name": "James O Lindsay"
    },
    {
      "affiliations": [
        "Yeovil Hospital, Yeovil, UK"
      ],
      "name": "Katie Smith"
    },
    {
      "affiliations": [
        "St Mark’s the National Bowel Hospital, London, UK"
      ],
      "name": "Naila Arebi"
    },
    {
      "affiliations": [
        "Huddersfield Royal Infirmary, Huddersfield, UK"
      ],
      "name": "Mohamed Yousif"
    },
    {
      "affiliations": [
        "The Ulster Hospital, Belfast, UK"
      ],
      "name": "Darragh McCullagh"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "Nick Powell"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Jessica Huskey"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Laurence Desroys du Roure"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Zineb Kaiss"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Fabio Cataldi"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Doug Jacobstein"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Christopher J Rabbat"
    },
    {
      "affiliations": [
        "Abivax, Paris, France"
      ],
      "name": "Kevin Shan"
    },
    {
      "affiliations": [
        "IRCCS Ospedale, San Raffaele, Italy"
      ],
      "name": "Silvio Danese"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, USA"
      ],
      "name": "Bruce E Sands"
    }
  ],
  "title": "O61 Efficacy and safety of obefazimod in moderate-to-severe ulcerative colitis: 8-week phase 3 ABTECT induction trial results",
  "uid": "d487c08b-fbb1-57dd-8f96-ddd8244f0741"
}