Celldex Therapeutics Shows Barzolvolimab Phase 2 Study Results in Angioedema Improvement at EAACI 2024

Celldex Therapeutics, Inc. has released new data from a Phase 2 clinical trial of barzolvolimab, showing significant improvements in angioedema symptoms for patients with chronic spontaneous urticaria (CSU). The results were presented by Dr. Marcus Maurer, a Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin, during the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024. The study demonstrated that barzolvolimab, a humanized monoclonal antibody, offers rapid, substantial, and durable relief from angioedema.

Angioedema, a swelling of the deeper skin layers and mucous membranes, severely affects the quality of life for CSU patients. It commonly targets the face, hands, feet, and genitalia, and can also involve areas such as the tongue and throat. This condition is particularly debilitating and painful for those who suffer from severe CSU.

Celldex's Phase 2 study involved 208 patients who were randomized to receive different doses of barzolvolimab or a placebo over a 16-week period. The doses were 75 mg every 4 weeks, 150 mg every 4 weeks, and 300 mg every 8 weeks. After the initial 16 weeks, patients entered a 36-week active treatment phase, where some were re-randomized to continue on barzolvolimab at varying doses.

Key findings from the study include:
- Significant reductions in the weekly angioedema activity score (AAS7) across all barzolvolimab dose groups compared to placebo.
- Rapid onset of improvement within two weeks, which was sustained through 12 weeks.
- Greater than 8-point improvements in AAS7 for a majority of patients, indicating a clinically meaningful benefit.
- Increased days without angioedema, particularly notable in the 300 mg cohort, which experienced 77% angioedema-free days over 12 weeks.

The study also highlighted that barzolvolimab was effective regardless of a patient's previous treatment history with omalizumab, an anti-IgE treatment commonly used for CSU. Approximately 20% of the study participants had received prior treatment with omalizumab, and over half of these had refractory disease. These patients exhibited similar benefits from barzolvolimab as those naïve to omalizumab.

The primary endpoint of the study was the change in the weekly urticaria activity score (UAS7) at week 12. Secondary endpoints included other safety and clinical activity assessments, such as weekly itch severity score (ISS7) and weekly hives severity score (HSS7), alongside the weekly angioedema activity score (AAS7).

Barzolvolimab works by targeting and inhibiting the activity of the receptor tyrosine kinase KIT, which is involved in the activation and function of mast cells. Mast cells play a pivotal role in inflammatory responses, including those seen in chronic urticaria.

Given the promising results, Celldex plans to advance barzolvolimab into Phase 3 trials in the summer, aiming to establish it as a transformative treatment for patients with CSU. The company believes that barzolvolimab has the potential to significantly improve the lives of those suffering from severe inflammatory and allergic conditions.

In conclusion, the Phase 2 trial data underscores barzolvolimab's potential as an effective treatment for CSU, offering rapid and durable relief from angioedema while demonstrating a favorable safety profile. These findings pave the way for further clinical development and potential future approval as a novel therapy for chronic spontaneous urticaria and other inflammatory diseases.