2. Academic Validation
  3. Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria

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

  • Allergy. 2022 Nov 16. doi: 10.1111/all.15585.
Dorothea Terhorst-Molawi 1 2,  Tomasz Hawro 3,  Eva Grekowitz 1 2,  Lea Kiefer 1 2,  Kunal Merchant 4,  Diego Alvarado 4,  Lawrence J Thomas 4,  Thomas Hawthorne 4,  Elizabeth Crowley 4,  Margo Heath-Chiozzi 4,  Martin Metz 1 2,  Marcus Maurer 1 2
Affiliations

Affiliations

  • 1 Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • 2 Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
  • 3 Department of Dermatology, Allergology and Venereology, Institute and Comprehensive Center for Inflammation Medicine, University Medical Center Schleswig-Holstein, Lübeck, Germany.
  • 4 Celldex Therapeutics, Hampton, New Jersey, USA.
PMID: 36385701 DOI: 10.1111/all.15585
Abstract

Background: 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.

Methods: 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).

Results: Analysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 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% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD), and all (n = 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.

Conclusion: 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.

Keywords

CDX-0159; barzolvolimab; chronic inducible urticaria; cold urticaria; symptomatic dermographism.

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