Recent Study Highlights Efficacy of Barzolvolimab in Treating Chronic Spontaneous Urticaria
A recent study published in the *European Journal of Allergy and Clinical Immunology* has shown that Barzolvolimab, a monoclonal anti-KIT antibody, significantly reduces symptoms in patients with moderate to severe antihistamine-refractory chronic spontaneous urticaria (CSU) . This marks a promising development in the treatment of a condition that has limited therapeutic options and severely impacts patients’ quality of life.
Background and Methods
Chronic spontaneous urticaria (CSU) is a mast cell–mediated disease characterized by itchy wheals and/or angioedema without identifiable triggers. It can persist for years or even decades, significantly affecting patients’ daily activities, work performance, sleep quality, social functioning, and mental health . Current treatments often fail to provide complete symptom control, especially in patients who do not respond adequately to antihistamines or omalizumab .
Barzolvolimab (CDX-0159) is a first-in-class anti-KIT monoclonal antibody that depletes mast cells by inhibiting the activation of KIT by stem cell factor. Previous studies have shown its efficacy in reducing disease activity and skin mast cells in patients with chronic inducible urticaria . This phase 1b, double-blind, randomized study (NCT04538794) evaluated the safety, pharmacokinetics, and pharmacodynamics of Barzolvolimab in adults with CSU. The study included a 2-week screening phase,12weeks of treatment, and a 12-week follow-up. Participants were assigned to receive Barzolvolimab or placebo on one of two dosing schedules: every 4 or 8 weeks.
Findings
A total of 93.3% (42 out of 45) of participants completed the 12-week treatment phase. The majority of participants in the Barzolvolimab group were female. with a median age of 49.3 years. The duration of CSU varied widely among participants, ranging from 0.6 years to over 6 decades.
Barzolvolimab demonstrated robust and sustained suppression of serum tryptase, a marker of mast cell activation. Within days of the initial dose, tryptase levels dropped by over 90% in the 1.5 mg/kg and higher-dose cohorts and remained suppressed throughout the 12-week dosing period. Clinically meaningful reductions in disease severity were observed across all Barzolvolimab-treated cohorts. By week 12, average UAS7 scores (a measure of urticaria activity) declined substantially, with the 3.0 mg/kg and 4.5 mg/kg groups experiencing reductions of 30 to 35 points compared to baseline. In contrast, placebo-treated patients showed minimal change.
A significant proportion of patients receiving 3.0 mg/kg and 4.5 mg/kg Barzolvolimab achieved near-complete or complete symptom control. Over 60% of patients in the highest-dose group reached UAS7 scores below 6 by the end of the treatment period, indicating well-controlled dise
ase. These rates were notably higher than in placebo recipients, none of whom reached full disease control.
Barzolvolimab was generally well-tolerated, with adverse events being mostly mild to moderate in severity. The most common adverse event was hair color change, reported in 26% of Barzolvolimab-treated patients. No indication of cumulative toxicity or worsening safety profile was observed with ascending doses.
Conclusions
The study authors concluded that Barzolvolimab shows promise as a novel treatment for antihistamine-refractory CSU, offering rapid and sustained symptom reduction. However, they noted limitations, including the small sample size and variation in prior medications used by participants. Future large-scale studies are needed to further evaluate Barzolvolimab’s efficacy and safety in CSU and other mast cell-driven diseases. Global Phase 3 studies for Barzolvolimab in CSU are currently enrolling, with plans to advance the drug into Phase 3 development for chronic inducible urticaria (CIndU) in 2025.
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