Celldex Therapeutics announced positive results from its Phase 2 clinical trial of barzolvolimab in patients with chronic inducible urticaria (CIndU), specifically cold urticaria (ColdU) and symptomatic dermographism (SD), who remain symptomatic despite antihistamine treatment. The study met all primary and secondary endpoints with high statistical significance, demonstrating clinically meaningful improvements in patients' trigger thresholds and overall disease control. The company plans to initiate Phase 3 development in 2025.
Efficacy and Clinical Significance
The Phase 2 trial randomized 196 patients with CIndU refractory to antihistamines to receive either 150 mg of barzolvolimab every 4 weeks, 300 mg every 8 weeks, or placebo. The primary endpoint was the percentage of patients with a negative provocation test at Week 12, assessed using the TempTest® for ColdU and the FricTest® for SD. Key secondary endpoints included responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CTT and CFT), changes in WI-NRSprovo (itch associated with provocation test), and Urticaria Control Test (UCT) scores.
The results showed that barzolvolimab significantly improved patient outcomes compared to placebo. In cold urticaria patients, 46.9% (150 mg q4w) and 53.1% (300 mg q8w) achieved a negative provocation test (complete response) compared to 12.5% in the placebo group (p=0.0023 and p=0.0011, respectively). Similarly, in symptomatic dermographism patients, 57.6% (150 mg q4w) and 42.4% (300 mg q8w) achieved a negative provocation test compared to 3.2% in the placebo group (p<0.0001 and p=0.0003, respectively).
Dr. Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics, stated, "Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria and we are excited to report that all primary and secondary endpoints across the study were highly statistically significant and clinically meaningful."
Safety and Tolerability
Barzolvolimab demonstrated a favorable safety profile, with most adverse events being Grade 1 (mild). The most common treatment-emergent adverse events were hair color changes (13%) and neutropenia (10%), which are mechanism-related (KIT) and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo, with no association between neutropenia and infections. The study had a high completion rate, with 90% of patients completing the study through 12 weeks.
Mechanism of Action and Target Population
Barzolvolimab is a humanized monoclonal antibody that binds to the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in mast cells, which mediate inflammatory responses in conditions like chronic urticaria. By inhibiting KIT, barzolvolimab aims to reduce mast cell activation and alleviate the symptoms of CIndU. This mechanism of action could provide a targeted therapy for patients who do not respond adequately to antihistamines, the current standard of care.
Future Directions
Celldex plans to advance barzolvolimab into Phase 3 development for CIndU in 2025. The company is also studying barzolvolimab in other inflammatory diseases, including chronic spontaneous urticaria (CSU), prurigo nodularis (PN), and eosinophilic esophagitis (EoE), with plans to explore additional indications such as atopic dermatitis (AD).
