Celldex Reports Positive Phase 2 Results for Barzolvolimab in Chronic Inducible Urticaria

Celldex Therapeutics, Inc. (NASDAQ: CLDX) announced promising topline results from its Phase 2 clinical trial of barzolvolimab for two prevalent forms of chronic inducible urticaria (CIndU)—cold urticaria (ColdU) and symptomatic dermographism (SD). The study targeted patients still symptomatic despite antihistamine treatments. Barzolvolimab, a humanized monoclonal antibody, specifically targets and inhibits the receptor tyrosine kinase KIT, a critical component in mast cell function and survival. CIndU is marked by hives triggered by specific stimuli—cold exposure in ColdU and skin rubbing in SD—where mast cell activation is a key factor.

Anthony S. Marucci, President and CEO of Celldex Therapeutics, highlighted the significance of barzolvolimab as the first drug to show statistically significant and clinically meaningful results in a large, randomized, placebo-controlled CIndU study. Marucci emphasized the unmet need for new treatments in this debilitating condition, which causes severe itching and burning hives that significantly disrupt patients' lives. He expressed gratitude to the study participants and investigators and announced plans to present the full 12-week data at an upcoming medical conference later this year.

The study involved 196 patients who were randomized to receive either barzolvolimab or a placebo. Results showed that barzolvolimab met its primary efficacy endpoint, demonstrating a statistically significant difference in the percentage of patients with a negative provocation test at Week 12 compared to placebo, as measured by the TempTest® for ColdU and FricTest® for SD. Barzolvolimab also showed rapid, durable, and clinically meaningful responses in patients with CIndU unresponsive to antihistamines. Patient demographics and baseline characteristics were similar across treatment groups.

Regarding safety, barzolvolimab was well tolerated, with a safety profile similar to previous studies. Most adverse events were mild to moderate. In the first 12 weeks, the most common adverse events in barzolvolimab-treated patients were hair color changes (13%) and neutropenia (11%). There was a comparable rate of infections between the barzolvolimab and placebo groups, with no link between neutropenia and infections.

The Phase 2 clinical trial was designed to assess the efficacy and safety of two dosing regimens of barzolvolimab in CIndU patients who remained symptomatic despite antihistamine therapy. The trial enrolled 196 patients, divided into two cohorts based on CIndU subtype. The participants, including 97 with ColdU and 99 with SD, were randomized into three groups to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo over a 20-week treatment period. This was followed by a 24-week follow-up phase. The primary endpoint was the percentage of patients with a negative provocation test at Week 12. Secondary endpoints included safety and other clinical activity assessments such as CTT (critical temperature threshold), CFT (critical friction threshold), and WI-NRS (worst itch numeric rating scale).

Chronic inducible urticarias, affecting about 0.5% of the population, are characterized by hives or wheals triggered by specific stimuli. ColdU symptoms include itching, burning hives, and angioedema in response to cold, while SD symptoms involve hives due to skin rubbing. Currently, there are no approved therapies for these conditions beyond antihistamines, and patients often manage symptoms by avoiding triggers.

Barzolvolimab binds with high specificity to the receptor tyrosine kinase KIT, effectively inhibiting its activity. KIT is crucial for the function and survival of mast cells, which are involved in inflammatory and allergic reactions. In diseases like chronic urticaria, mast cell activation is central to disease onset and progression. Barzolvolimab is also being researched for chronic spontaneous urticaria (CSU), prurigo nodularis (PN), and eosinophilic esophagitis (EOE), with plans to explore additional indications such as atopic dermatitis (AD).

Celldex Therapeutics is a clinical-stage biotech company focused on mast cell biology and the development of transformative therapeutics for severe inflammatory, allergic, autoimmune, and other impactful diseases. Their pipeline includes antibody-based therapies designed to engage the immune system and target critical pathways to improve patient outcomes.

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