{
  "abstract": "Objectives Cutaneous manifestations of lupus are common, yet effective therapies targeting the underlying pathogenesis are lacking. Toll-like receptors (TLR) 7/8 are key upstream drivers of the interferon pathway and neutrophil, myeloid cell and B cell activation. Enpatoran is a novel, first-in-class, oral TLR7/8 inhibitor. In a Phase 2 randomised, double-blind, placebo-controlled study (WILLOW [ NCT05162586]), enpatoran reduced disease activity in participants with cutaneous manifestations of CLE/SLE (Cohort A) or moderate-to-severe SLE (Cohort B), with high rates of CLASI-50/CLASI-70 responses, and was well tolerated. We report pooled safety and tolerability in the subgroup of participants with cutaneous manifestations in Cohorts A and B.Methods Safety of enpatoran was evaluated from Day 1 to the end of safety follow-up at Week 26 ( figure 1), according to the pre-defined secondary endpoints of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), adverse events of special interest (AESIs), abnormal (grade 3) laboratory values, and clinically important increases in QT interval corrected using Fridericia’s Formula (QTcF). Cutaneous manifestations of lupus were defined as CLASI-A >=8 at screening and baseline.Results Safety data from 265 participants with cutaneous manifestations were included. The incidence of treatment-related TEAEs was marginally higher with enpatoran versus placebo, but did not increase with increasing enpatoran dose ( table 1). One treatment-related SAE was reported (herpes zoster infection in the enpatoran 100 mg BID group). No TEAEs led to death in any treatment group. The most frequently reported treatment-related TEAEs were infections and infestations, gastrointestinal disorders, and investigations and were more often reported with enpatoran than placebo (table 1). Three (3.8%) participants reported >=1 AESI, all in the enpatoran 100 mg BID group. Decreased lymphocyte count was more common with placebo (n=4; 5.9%) than enpatoran 25 mg BID (n=1; 1.9%), 50 mg BID (n=2; 3.1%) or 100 mg BID (n=2; 2.5%). No clinically relevant between-group differences were observed in other laboratory parameters, vital signs, or electrocardiogram findings including QTcF.Abstract S1:04 Figure 1Abstract S1:04 Table 1Pooled safety data from WILLOW cohorts A and B for participants with CLE/SLE and cutaneous manifestationsaConclusions Enpatoran was well tolerated across all doses in participants with cutaneous manifestations of lupus at baseline in the WILLOW study, consistent with the overall study population and other previous studies of enpatoran, with no new safety concerns identified.",
  "authors": [
    {
      "affiliations": [
        "Centre for Inflammatory Diseases, Monash University, Melbourne, VIC, Australia"
      ],
      "name": "Eric Morand"
    },
    {
      "affiliations": [
        "Department of Dermatology, Perelman School of Medicine, University of Pennsylvania and Philadelphia VAMC, Philadelphia, PA, USA"
      ],
      "name": "Victoria P Werth"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Northwell Health, Great Neck, NY, USA"
      ],
      "name": "Richard Furie"
    },
    {
      "affiliations": [
        "Ares Trading SA, an affiliate of Merck KGaA, Eysins, Switzerland"
      ],
      "name": "Sanjeev Roy"
    },
    {
      "affiliations": [
        "EMD Serono Research and Development Institute, Inc., an affiliate of Merck KGaA, Billerica, MA, USA"
      ],
      "name": "Ruth Fernandez-Ruiz"
    },
    {
      "affiliations": [
        "EMD Serono Research and Development Institute, Inc., an affiliate of Merck KGaA, Billerica, MA, USA"
      ],
      "name": "Summer G Goodson"
    },
    {
      "affiliations": [
        "Merck Healthcare KGaA, Darmstadt, Germany"
      ],
      "name": "Hans Gühring"
    },
    {
      "affiliations": [
        "EMD Serono Research and Development Institute, Inc., an affiliate of Merck KGaA, Billerica, MA, USA"
      ],
      "name": "Flavie Moreau"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Minnesota, Minneapolis, MN, USA"
      ],
      "name": "David R Pearson"
    }
  ],
  "title": "S1:04 Enpatoran, a toll-like receptor 7/8 inhibitor, in skin manifestations of cutaneous lupus erythematosus or systemic lupus erythematosus: pooled safety data from the phase 2 willow trial",
  "uid": "a18c84cd-2a83-5ea8-9604-818b91d81de6"
}