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

• DOI: 10.1111/all.15585
• Publication Date: 2022-11-17T07:59:56Z
• Authors: Dorothea Terhorst...; Tomasz Hawro; Eva Grekowitz; Lea Kiefer; Kunal Merchant; Diego Alvarado; Lawrence J. Thomas; Thomas Hawthorne; Elizabeth Crowley; Margo Heath‐Chiozzi; Martin Metz; Marcus Maurer
• Keywords: Tryptase; Tolerability; Pharmacodynamics; Clinical endpoint

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