{
  "abstract": "Objective To evaluate multiple-ascending doses of enpatoran, a selective toll-like receptor 7/8 (TLR7/8) inhibitor with the potential to modulate processes central to lupus pathophysiology, in patients with systemic and cutaneous lupus erythematosus (SLE/CLE).Methods In this randomised, double-blind, placebo-controlled phase Ib trial ( NCT04647708), patients with active SLE/CLE were randomised 3:1 to enpatoran or placebo across four cohorts. Treatment duration was 12/24 weeks. All patients had a 2-week safety follow-up. The primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetics (PK) and clinical response. Change in lupus biomarkers, including interferon gene signature (IFN-GS), was an exploratory endpoint.Results 25 patients received placebo (n=6) or enpatoran (n=19); 80% were female, all were white, and the median age was 44 years. By week 12, treatment-emergent adverse events (TEAEs) were reported by 42% of patients across the four enpatoran dose groups and 33% of placebo-treated patients. Enpatoran remained well tolerated to week 24. Most TEAEs (96%) were mild or moderate in severity. There were no serious TEAEs. Enpatoran PK was dose proportional, with peak concentration reached 1–2 hours postdose and an apparent half-life of 6–10 hours across doses. Greater reductions in Systemic Lupus Erythematosus Disease Activity Index 2000, Physician’s Global Assessment and 28-joint count were observed at week 24 with enpatoran versus placebo. Rapid, dose-dependent and reversible suppression of IFN-GS was observed.Conclusions Enpatoran was well tolerated and demonstrated favourable safety and PK profiles in patients with SLE and CLE. Although preliminary, the SLE disease activity and biomarker results support the therapeutic targeting of TLR7/8 for lupus.Trial registration number NCT04647708.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany"
      ],
      "name": "Torsten Witte"
    },
    {
      "affiliations": [
        "EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"
      ],
      "name": "Ruth Fernandez-Ruiz"
    },
    {
      "affiliations": [
        "Merck Healthcare KGaA, Darmstadt, Germany"
      ],
      "name": "Nadezda Abramova"
    },
    {
      "affiliations": [
        "Merck Healthcare KGaA, Darmstadt, Germany"
      ],
      "name": "Dominika Weinelt"
    },
    {
      "affiliations": [
        "EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"
      ],
      "name": "Flavie Moreau"
    },
    {
      "affiliations": [
        "Merck Healthcare KGaA, Darmstadt, Germany"
      ],
      "name": "Lena Klopp-Schulze"
    },
    {
      "affiliations": [
        "EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"
      ],
      "name": "Jamie Shaw"
    },
    {
      "affiliations": [
        "EMD Serono Research & Development Institute, Inc. (an affiliate of Merck KGaA), Billerica, Massachusetts, USA"
      ],
      "name": "Deborah Denis"
    },
    {
      "affiliations": [
        "Department of Dermatology and Allergy, University Hospital of Bonn, Bonn, Germany"
      ],
      "name": "Joerg Wenzel"
    }
  ],
  "title": "Enpatoran, a first-in-class, selective, orally administered toll-like receptor 7/8 inhibitor, in systemic and cutaneous lupus erythematosus: results from a randomised, placebo-controlled phase Ib study",
  "uid": "9769eb01-2919-5275-b3f1-247818f1024f"
}