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

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...

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Published in:Allergy (Copenhagen) 2023-05, Vol.78 (5), p.1269-1279
Main Authors: Terhorst‐Molawi, Dorothea, Hawro, Tomasz, Grekowitz, Eva, Kiefer, Lea, Merchant, Kunal, Alvarado, Diego, Thomas, Lawrence J., Hawthorne, Thomas, Crowley, Elizabeth, Heath‐Chiozzi, Margo, Metz, Martin, Maurer, Marcus
Format: Article
Language:English
Subjects:
Antihistamines
barzolvolimab
CDX‐0159
Cell activation
Chronic Disease
Chronic Inducible Urticaria
cold urticaria
Disease control
Humans
Mast cells
Mast Cells - pathology
Patients
Pharmacodynamics
Proto-Oncogene Proteins c-kit
Provocation tests
Quality of Life
Receptor mechanisms
Skin diseases
Skin tests
Stem cell factor
symptomatic dermographism
Tryptase
Tryptases
Urticaria
Urticaria - diagnosis
Urticaria - drug therapy
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Summary: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 (
ISSN:0105-4538
1398-9995
DOI:10.1111/all.15585