{
  "abstract": "Background/Objectives Frexalimab, a second-generation anti-CD40L antibody, blocks the CD40/CD40L pathway, which is important in regulating adaptive and innate immunity. During the 12-week (W) double-blind period of the phase-2 trial ( NCT04879628) in participants with relapsing multiple sclerosis (pwRMS), frexalimab was well-tolerated and efficacious, with 1200-mg intravenous (IV) arm showing an 89% reduction in new gadolinium-enhancing (Gd+) T1-lesions vs placebo. Here, we report W96 results in the open-label extension (OLE).Methods 129 participants were randomised (4:4:1:1) to frexalimab 1200mg/IV every-4-weeks (q4w) or frexalimab300mg/subcutaneous (SC) q2w or matching placebo. After W12, participants receiving placebo switched to frexalimab arms. During OLE, the SC dose was increased to 1800-mg q4w, resulting in similar frexalimab exposure as with 1200-mg q4w IV dose; 36/57 participants in SC arms received high-dose and underwent W96 MRI assessments. Key endpoints: safety and efficacy (Gd+ T1-lesions, new/enlarging T2-lesions, annualised relapse rate [ARR]).Results 106 participants (82%) remained on treatment at W96. Total number of Gd+ T1-lesions (mean±SD) remained low at W96 in participants who continued receiving frexalimab and who switched from placebo to frexalimab at W12 (IV arms: frexalimab 1200mg/IV: 0.1±0.5, placeboIV/frexalimab1200mg/IV: 0.1±0.3; all SC arms: ≤0.4). New/enlarging T2-lesion monthly count remained low with frexalimab1200mg/IV through W96. ARR (baseline-W96) was low (0.08 [95% CI, 0.03–0.18]) in frexalimab1200mg/IV arm; 92% of participants were relapse-free. Most common adverse events were nasopharyngitis, headache, and COVID-19.Conclusions Frexalimab continues to show favourable safety and sustained reduction in disease activity in pwRMS through W96, supporting its further development in phase-3 trials as a potential high-efficacy, non-lymphocyte-depleting therapy.",
  "authors": [
    {
      "affiliations": [
        "University of Lille, Inserm U1172, Lille Neuroscience and Cognition, CHU Lille, FHU Precise, Lille, France"
      ],
      "name": "Patrick Vermersch"
    },
    {
      "affiliations": [
        "Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland"
      ],
      "name": "Cristina Granziera"
    },
    {
      "affiliations": [
        "Autoimmunity Center of Excellence, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA"
      ],
      "name": "Yang Mao-Draayer"
    },
    {
      "affiliations": [
        "Department of Biostatistics, UAB School of Public Health, Birmingham, AL, USA"
      ],
      "name": "Gary Cutter"
    },
    {
      "affiliations": [
        "Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine"
      ],
      "name": "Oleksandr Kalbus"
    },
    {
      "affiliations": [
        "Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria"
      ],
      "name": "Ivan Staikov"
    },
    {
      "affiliations": [
        "First Department of Neurology, St. Anne’s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic"
      ],
      "name": "Michal Dufek"
    },
    {
      "affiliations": [
        "Multiple Sclerosis Centre of Catalonia, Department of Neurology, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Xavier Montalban"
    },
    {
      "affiliations": [
        "Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, USA"
      ],
      "name": "Stephen Krieger"
    },
    {
      "affiliations": [
        "Sanofi, Gentilly, France"
      ],
      "name": "Stephane Saubadu"
    },
    {
      "affiliations": [
        "Sanofi, Bridgewater, NJ, USA"
      ],
      "name": "Xiaodong Luo"
    },
    {
      "affiliations": [
        "Sanofi, Bridgewater, NJ, USA"
      ],
      "name": "Brendan Smyth"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, MA, USA"
      ],
      "name": "Biljana Djukic"
    },
    {
      "affiliations": [
        "Sanofi, Gentilly, France"
      ],
      "name": "Philippe Truffinet"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, MA, USA"
      ],
      "name": "Erik Wallstroem"
    },
    {
      "affiliations": [
        "Queen Mary University of London, London, UK"
      ],
      "name": "Gavin Giovannoni"
    },
    {
      "affiliations": [
        "Department of Neurology, Austin Hospital, Austin Health, Heidelberg, VIC, Australia"
      ],
      "name": "Marion Simpson"
    }
  ],
  "title": "3462 Safety and efficacy of frexalimab from the phase 2 open-label extension in participants with relapsing multiple sclerosis: 2-year results",
  "uid": "ed36d8c3-6534-55d2-8a03-8fd92e7d2677"
}