Anti‐KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria

  • Dorothea Terhorst‐Molawi
    Institute of Allergology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany
  • Tomasz Hawro
    Department of Dermatology, Allergology and Venereology, Institute and Comprehensive Center for Inflammation Medicine University Medical Center Schleswig‐Holstein Lübeck Germany
  • Eva Grekowitz
    Institute of Allergology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany
  • Lea Kiefer
    Institute of Allergology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany
  • Kunal Merchant
    Celldex Therapeutics Hampton New Jersey USA
  • Diego Alvarado
    Celldex Therapeutics Hampton New Jersey USA
  • Lawrence J. Thomas
    Celldex Therapeutics Hampton New Jersey USA
  • Thomas Hawthorne
    Celldex Therapeutics Hampton New Jersey USA
  • Elizabeth Crowley
    Celldex Therapeutics Hampton New Jersey USA
  • Margo Heath‐Chiozzi
    Celldex Therapeutics Hampton New Jersey USA
  • Martin Metz
    Institute of Allergology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany
  • Marcus Maurer
    Institute of Allergology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt‐Universität zu Berlin Berlin Germany

抄録

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)‐mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX‐0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose‐dependent plasma tryptase suppression indicative of systemic mast cell ablation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This is an open‐label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12‐week follow‐up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Analysis populations were safety (<jats:italic>n</jats:italic> = 21) and pharmacodynamics/clinical activity (<jats:italic>n</jats:italic> = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (<limit of detection), and increased soluble SCF through Week 12. Complete responses (negative provocation test) occurred in 95% (<jats:italic>n</jats:italic> = 19/20) of patients (<jats:italic>n</jats:italic> = 10/10 ColdU; <jats:italic>n</jats:italic> = 9/10 SD), and all (<jats:italic>n</jats:italic> = 20/20) showed improvement in urticaria control (UCT ≥ 12). The kinetics of clinical activity mirrored that of MC and tryptase reduction. DLQI‐measured impairment significantly decreased to minimal/none in 93% of patients on study.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In CIndU patients, barzolvolimab was well tolerated, demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, and reductions in clinical activity with significant improvements in disease control and quality of life (QoL) demonstrating potential therapeutic effects for MC‐mediated disorders.</jats:p></jats:sec>

収録刊行物

  • Allergy

    Allergy 78 (5), 1269-1279, 2022-12-03

    Wiley

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