Anti-KIT Barzolvolimab for Chronic Spontaneous Urticaria

Area of Science:

• Immunology
• Dermatology
• Pharmacology

Background:

• Chronic spontaneous urticaria (CSU) is a mast cell (MC)-mediated condition causing wheals and angioedema without clear triggers.
• Barzolvolimab, an anti-KIT monoclonal antibody, targets MC activation by inhibiting stem cell factor binding, leading to MC depletion.

Purpose of the Study:

• To evaluate the safety and efficacy of multiple ascending doses of barzolvolimab in patients with moderate-to-severe antihistamine-refractory CSU.
• To assess disease activity using UAS7 and UCT scores, alongside pharmacokinetic and pharmacodynamic profiles.

Main Methods:

• Phase 1b, double-blind, placebo-controlled trial involving four sequentially enrolled cohorts of adults with CSU.
• Patients received intravenous barzolvolimab (0.5, 1.5, 3, or 4.5 mg/kg) or placebo every 4 or 8 weeks for 12 weeks, followed by a 12-week follow-up.
• Primary endpoints were safety and disease activity (UAS7, UCT); pharmacokinetics and pharmacodynamics were also assessed.

Main Results:

• Barzolvolimab was well-tolerated, with hair color change as the most common adverse event.
• Rapid and sustained symptom reduction was observed within 1 week, with 71% achieving well-controlled CSU (UAS7 ≤ 6) and 57% achieving complete response (UAS7 = 0) by Week 12.
• Significant improvements in UCT scores were noted, with 77% achieving well-controlled status (UCT ≥ 12) and 43% achieving complete response (UCT = 16). Disease activity changes correlated with tryptase suppression, indicating MC inhibition.

Conclusions:

• Barzolvolimab demonstrated a favorable safety profile and significant efficacy in reducing CSU symptoms.
• The study supports barzolvolimab as a promising therapeutic option for patients with chronic spontaneous urticaria.
• Efficacy was consistent across different dosing regimens and in patients with or without prior omalizumab treatment.