Celldex's Barzolvolimab Phase 2 Study Delivers Positive News For Chronic Inducible Urticaria Patients

Celldex Therapeutics, Inc., has announced encouraging topline findings from its Phase 2 clinical trial investigating barzolvolimab for two prevalent types of chronic inducible urticaria (CIndU)—cold urticaria (ColdU) and symptomatic dermographism (SD). This trial involved patients who continue to experience symptoms despite receiving antihistamine treatment.

Barzolvolimab is a humanized monoclonal antibody that targets the receptor tyrosine kinase KIT with remarkable specificity, effectively inhibiting its function, which is essential for the survival and activity of mast cells. CIndU is defined by the emergence of hives or wheals triggered by specific factors: exposure to cold temperatures in ColdU and skin irritation from scratching or rubbing in SD. Mast cell activation plays a pivotal role in the pathophysiology of both ColdU and SD.

Anthony S. Marucci, President & Chief Executive Officer of Celldex Therapeutics, said in a statement “Barzolvolimab is the first drug in development to demonstrate statistically significant and clinically meaningful results in a large, randomized, placebo-controlled study in chronic inducible urticaria. These data are unprecedented and clearly demonstrate that barzolvolimab has the potential to become a critically needed new treatment option for patients suffering from this disease.”

He further added, “Inducible urticaria is a disease of misery for patients who despite their best efforts 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. We look forward to advancing barzolvolimab into registrational studies in inducible urticaria and moving towards our goal of bringing this potential new medicine to patients. We would like to thank the patients and investigators who participated in this study and look forward to presenting the full 12 week data from this study at an upcoming medical meeting in the fourth quarter of this year.”

The study involving 196 randomized patients indicated that barzolvolimab met the primary efficacy endpoint, showing a statistically significant improvement in the percentage of patients with a negative provocation test compared to the placebo at Week 12, as evaluated by the TempTest® in ColdU and the FricTest® in SD. Notably, barzolvolimab exhibited quick, lasting, and clinically relevant responses in patients with cold-induced urticaria (CIndU) who were resistant to antihistamines. Additionally, demographic and baseline disease characteristics were comparable among the treatment groups.

Barzolvolimab demonstrated good tolerability and a safety profile that aligns with previous research. The majority of adverse events were classified as mild to moderate. Over the 12-week period, the most frequently reported treatment-emergent adverse events among patients receiving barzolvolimab were changes in hair color (13%) and neutropenia (11%). The incidence of infections was comparable between the barzolvolimab and placebo groups, and no link was found between neutropenia and infection rates.

The Phase 2 trial is a randomized, double-blind, placebo-controlled, parallel-group study designed to assess the efficacy and safety of two dosing regimens of barzolvolimab in patients with cold-induced urticaria (CIndU) who continue to experience symptoms despite antihistamine treatment. A total of 196 patients were enrolled across two cohorts—97 with ColdU and 99 with symptomatic dermographism (SD)—and were randomly assigned in a 1:1:1 ratio to receive subcutaneous injections of either 150 mg of barzolvolimab every four weeks, 300 mg every eight weeks, or a placebo over a 20-week treatment period.

Following this, participants entered a 24-week follow-up phase. The primary endpoint of the study is the percentage of patients who achieve a negative provocation test at Week 12, using the TempTest® for ColdU and the FricTest® for SD. Secondary endpoints focus on safety and additional measures of clinical activity, including the critical temperature threshold (CTT), critical friction threshold (CFT), and worst itch numeric rating scale (WI-NRS).