Randomized dose-finding study of anti-KIT barzolvolimab in patients with chronic spontaneous urticaria

BACKGROUND: Chronic spontaneous urticaria (CSU) is characterized by wheals and/or angioedema without identifiable triggers. Mast cells play a pathogenic role in disease, but more evidence is needed to support their role in driving clinical manifestations. OBJECTIVE: We assessed the efficacy and safety of various dose regimens of barzolvolimab, a mast cell-depleting anti-KIT antibody, in patients with CSU. METHODS: Adults with antihistamine-refractory CSU (urticaria activity score over 7 days [UAS7] ≥ 16) in a phase 2 double-blind placebo-controlled trial were randomized 1:1:1:1 to receive barzolvolimab 75 mg every 4 weeks (n = 53); 150 mg every 4 weeks (n = 52); 300 mg every 8 weeks (n = 51); or placebo (n = 51). The primary end point was UAS7 change from baseline to week 12. RESULTS: There was significant improvement in mean (95% confidence interval) change from baseline to week 12 in UAS7 in barzolvolimab-treated patients compared to patients who received placebo (75 mg every 4 weeks: -6.60 [-10.71, -2.49] P = .0017; 150 mg every 4 weeks: -12.55 [-16.56, -8.55] P < .0001; 300 mg every 8 weeks: -13.41 [-17.47, -9.34] P < .0001). Clinical improvement was rapid and marked, with 22.9%, 51.1%, and 37.5% (75 mg, 150 mg, and 300 mg, respectively) of barzolvolimab-treated patients who experienced complete response (UAS7 = 0) versus 6.4% for placebo at 12 weeks. The disease of patients with and without prior omalizumab treatment responded similarly. All doses of barzolvolimab were well tolerated, with urticaria and hair color change as the most common adverse events in barzolvolimab-treated patients. CONCLUSION: This study provides evidence for the essential role of mast cells in the signs and symptoms of CSU. Barzolvolimab is a promising treatment for CSU. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT05368285.