Positive results from Phase II trial of barzolvolimab in chronic inducible urticaria- Cellldex Therapeutics

The study includes patients who remain symptomatic despite treatment with antihistamines. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. CIndU is characterized by the occurrence of hives or wheals that have an attributable trigger associated with them—exposure to cold temperatures in ColdU and scratching/rubbing of the skin in SD. Mast cell activation is known to be a critical driver in ColdU and SD.

The data were presented in a late breaking oral presentation at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting in Boston by Dr. Jonathan Bernstein, Professor of Clinical Medicine, Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, University of Cincinnati Medical Center and Partner, Bernstein Allergy Group and Clinical Research Center.

“Chronic inducible urticaria is a devastating disease for patients who despite constant vigilance often find it impossible to avoid their disease triggers and are impacted by severe itching and burning hives that dramatically impact all aspects of their lives,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “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. 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. We are actively working towards bringing this potential new medicine to patients and look forward to initiating Phase III development in inducible urticaria in 2025.”

Celldex previously reported that barzolvolimab achieved the primary efficacy endpoint of the study, a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at Week 12 as assessed by the TempTest in ColdU and the FricTest in SD. Today the Company reported that all secondary endpoints in the study were also achieved at Week 12 and strongly support the primary endpoint results, including responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT and CFT), changes in WI-NRSprovo (itch associated with provocation test) and Urticaria Control Test.

196 patients with CIndU refractory to antihistamines were randomized to the study and 193 patients were included in the full analysis (mITT) and safety set (3 patients randomized to the study were not treated). 90% (n=173) of patients on study completed the study through 12 weeks (discontinuation rate of 8% barzolvolimab compared to 14% placebo). Demographics and baseline disease characteristics were well balanced across treatment groups. In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins. UCT scores at baseline reflect poorly controlled disease.

Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).

Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). Through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (13%; Grade 1, n=15 / Grade 2, n=2) and neutropenia (10%; Grade 1, n=7 / Grade 2, n=6), 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.