Celldex Publishes Landmark 52-Week Results from Barzolvolimab Phase 2 Study in Chronic Urticaria at EADV 2024

Celldex Therapeutics, Inc. has unveiled new data showcasing the significant and sustained efficacy of barzolvolimab in treating chronic spontaneous urticaria (CSU) over a 52-week period. This immune-related condition is driven by mast cell activation, and barzolvolimab targets these cells by binding to the receptor tyrosine kinase KIT, thereby inhibiting its activity. This inhibition is crucial for mast cell function and survival. The findings were presented by Dr. Martin Metz at the EADV Congress 2024.

Dr. Metz emphasized the unprecedented efficacy of barzolvolimab in CSU, highlighting its potential to deliver complete symptom control, especially for patients unresponsive to current treatments, including those with omalizumab-refractory disease. The Phase 2 study demonstrated that barzolvolimab not only met its primary endpoint but also provided early, durable, and comprehensive symptom relief. Importantly, the drug was well tolerated throughout the 52-week treatment period, underscoring its potential as a transformative therapy for CSU patients.

The Phase 2 study assessed barzolvolimab's performance over 52 weeks, noting significant improvements in the weekly urticaria activity score (UAS7) as early as the first week, with sustained or deepening responses by Week 52. After 16 weeks, patients initially on lower doses or placebo were transitioned to higher doses of barzolvolimab, resulting in similarly meaningful disease responses as the rest of the cohort. Notably, 71% of patients on a 150 mg dose every four weeks achieved complete response by Week 52, with early and sustained effects. Another 52% of patients on a 300 mg dose every eight weeks also achieved a complete response.

Further data showed that 74% of patients on the 150 mg dose and 68% on the 300 mg dose had well-controlled urticaria by the end of the study. These findings were consistent across patients with previous omalizumab experience, reinforcing barzolvolimab's broad applicability.

Barzolvolimab is a humanized monoclonal antibody that binds to the KIT receptor with high specificity, effectively inhibiting its role in mast cell activity. This mechanism is pivotal in managing inflammatory responses such as those seen in chronic urticaria. The drug is currently being investigated for multiple conditions, including chronic inducible urticaria, prurigo nodularis, and eosinophilic esophagitis, with plans to expand to other indications like atopic dermatitis.

The Phase 2 study was a randomized, double-blind, placebo-controlled trial involving 208 patients with CSU unresponsive to antihistamine therapy. Participants received varying doses of barzolvolimab or placebo over a 16-week period, followed by an active treatment phase. At the 52-week mark, the drug had achieved its primary efficacy endpoint, demonstrating a statistically significant improvement in UAS7 scores across all dose levels.

Building on these promising results, Celldex has initiated a global Phase 3 program for barzolvolimab in CSU. This program includes two trials aimed at confirming the drug's efficacy and safety in adult patients who remain symptomatic despite antihistamine treatment, including those unresponsive to biologics.

Chronic spontaneous urticaria is characterized by persistent hives and swelling without identifiable triggers, leading to prolonged discomfort and inflammation. Current therapies often fall short, providing only partial relief to some patients. Celldex Therapeutics is dedicated to developing innovative treatments that address the root causes of such severe and debilitating diseases.

Celldex continues to lead in the field of mast cell biology, leveraging its expertise to develop antibody-based therapeutics that engage the immune system and target critical pathways, offering hope to patients with challenging inflammatory and allergic conditions.