Celldex Therapeutics announced positive results from its Phase 2 clinical trial of barzolvolimab in patients with cold urticaria (ColdU) and symptomatic dermographism (SD), two common forms of chronic inducible urticaria (CIndU). The study included patients who remained symptomatic despite treatment with antihistamines. The data were presented at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting.
Significant Efficacy Demonstrated
The Phase 2 trial met its primary efficacy endpoint, demonstrating a statistically significant difference in the percentage of patients with a negative provocation test compared to placebo at Week 12. In ColdU, this was assessed using the TempTest®, and in SD, the FricTest®. All secondary endpoints were also achieved at Week 12, supporting the primary endpoint results. These included responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT), changes in WI-NRSprovo (itch associated with provocation test), and Urticaria Control Test scores.
Detailed Clinical Results
In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C. In patients with symptomatic dermographism, baseline FricTest thresholds were an average of 3.6 out of 4 pins. Key results at Week 12 included:
- Cold Urticaria:
- 150 mg q4w: 46.9% of patients achieved a negative provocation test (p=0.0023)
- 300 mg q8w: 53.1% of patients achieved a negative provocation test (p=0.0011)
- Placebo: 12.5% of patients achieved a negative provocation test
- Symptomatic Dermographism:
- 150 mg q4w: 57.6% of patients achieved a negative provocation test (p<0.0001)
- 300 mg q8w: 42.4% of patients achieved a negative provocation test (p=0.0003)
- Placebo: 3.2% of patients achieved a negative provocation test
Safety and Tolerability
Barzolvolimab was well-tolerated, with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). The most common treatment-emergent adverse events in barzolvolimab-treated patients 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.
Mechanism of Action
Barzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in mast cells, which mediate inflammatory responses. By inhibiting KIT signaling, barzolvolimab controls the differentiation, tissue recruitment, survival, and activity of mast cells.
Future Plans
Celldex plans to advance barzolvolimab into Phase 3 development for inducible urticaria in 2025. This offers a potential new medicine to patients. The company is also studying barzolvolimab in chronic spontaneous urticaria (CSU), prurigo nodularis (PN), and eosinophilic esophagitis (EOE), with additional indications planned, including atopic dermatitis (AD).
Expert Commentary
"Chronic inducible urticaria is a devastating disease for patients... Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria," said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "We believe these study results achieve the goal of treatment for patients by dramatically improving their trigger thresholds and enabling them to regain control of their lives."
