{
  "abstract": "Objectives Toll-like receptor (TLR)7 is a pattern recognition receptor that contributes to SLE pathogenesis. DS-7011a is an anti-TLR7 monoclonal antibody (mAb) that inhibits TLR7 signaling. The aim of this study was to explore safety and PK and to detect initial efficacy of DS-7011a in SLE patients.Methods This was a randomized, placebo-controlled, double-blind Phase 1b/2 study [ NCT05638802]. Patients were: 1) globally enrolled and randomized 2:1 to DS-7011a or placebo; 2) required to have definite SLE according to the 2019 EULAR/ACR criteria, active CLE (CLASI-A score of at least 4), and no or inactive LN; 3) given DS-7011a (20 mg/kg) or placebo IV 3 times Q4W starting at Week 0; and 4) followed until Week 16 to assess treatment effect. Study primary objective was safety and secondary objectives were PK and initial efficacy. TEAE were safety endpoints. DS-7011a plasma concentrations were analyzed by Population PK to derive PK endpoints. CLASI-A was the main efficacy endpoint and IFN-I gene signature (GS) expression was scored to understand the mechanism of action. Statistics were descriptive.Results 25 patients were randomized and received at least one dose of DS-7011a (n=19) or placebo (n=6) ( table 1). DS-7011a decreased CLASI-A more than placebo with an effect that persisted until Week 16 [DS-7011a mean (SE) CLASI-A score change from Baseline to Week 16 = -10.1 (2.4), placebo = 1.0 (3.4); difference (95% CI) = -11.1 (-21.1, -1.0)] (figure 1) and was particularly remarkable in patients with chronic CLE or severe CLE or high IFN-I GS expression. CLASI-50 and CLASI-70 were 53% and 41% with DS-7011a, respectively, and both were 17% with placebo. DS-7011a also decreased CLA-IGA, SLEDAI-2K, and PGA-SLE more than placebo (figure 1). DS-7011a decreased IFN-I GS expression more than placebo, reducing it to levels close to those of healthy subjects. TEAE, none of which were severe, similarly occurred in patients treated with DS-7011a or placebo (table 2). No safety signal was identified. DS-7011a showed predictable PK typical of an IgG mAb, including long half-life.Abstract PO:11:280 Table 1–2Abstract PO:11:280 Figure 1Mean (#SE) CLASI-A, CLA-IGA, SLEDAI-2K, and PGA-SLE score changes from Baseline with DS-7011a and placebo^Conclusions DS-7011a was safe and well tolerated and showed favorable PK and initial efficacy. These results support DS-7011a further development for the treatment of SLE.",
  "authors": [
    {
      "affiliations": [
        "Daiichi Sankyo, Inc., Basking Ridge, NJ, USA"
      ],
      "name": "Giorgio Senaldi"
    },
    {
      "affiliations": [
        "Daiichi Sankyo, Inc., Basking Ridge, NJ, USA"
      ],
      "name": "Aparna Mohan"
    },
    {
      "affiliations": [
        "Daiichi Sankyo, Inc., Basking Ridge, NJ, USA"
      ],
      "name": "Yoshiaki Tomimori"
    },
    {
      "affiliations": [
        "Daiichi Sankyo, Inc., Basking Ridge, NJ, USA"
      ],
      "name": "Li Zhang"
    },
    {
      "affiliations": [
        "Daiichi Sankyo Co., Ltd., Tokyo, Japan"
      ],
      "name": "Naoki Miyoshi"
    },
    {
      "affiliations": [
        "Daiichi Sankyo, Inc., Basking Ridge, NJ, USA"
      ],
      "name": "Michael Grosso"
    },
    {
      "affiliations": [
        "Dept. of Rheumatology, Sts. Cyril and Methodius University, Skopje"
      ],
      "name": "Filip Gucev"
    },
    {
      "affiliations": [
        "Joint and Muscle Medical Care, Charlotte, NC, USA"
      ],
      "name": "Alireza Nami"
    },
    {
      "affiliations": [
        "Dept. of Dermatology, University of Minnesota, Minneapolis, MN, USA"
      ],
      "name": "David Pearson"
    },
    {
      "affiliations": [
        "Dept. of Molecular Targeted Therapeutics, University of Occupational and Environmental Health, Kitakyushu, Japan"
      ],
      "name": "Yoshiya Tanaka"
    }
  ],
  "title": "PO:11:280 Randomized, placebo-controlled, double-blind phase 1b/2 study to explore safety, pharmacokinetics, and initial efficacy of DS-7011a, an anti-toll-like receptor 7 monoclonal antibody, in SLE patients",
  "uid": "aa2fe21d-5578-5f05-811f-807b7a8c4f05"
}