Barzolvolimab Leads to Rapid, Sustained Improvements in CSU Over 52 Weeks

Martin Metz, MD

Credit: ADVENT Program

There are sustained and deepening disease improvements and a strong safety profile over the 52-week treatment with barzolvolimab in chronic spontaneous urticaria (CSU), according to recent findings presented at the European Academy of Dermatology & Venereology (EADV) Congress in Amsterdam.¹

These new data were announced by Celldex Therapeutics, Inc. and highlighted the effectiveness of barzolvolimab for CSU, an immune-related disease which is driven by mast cell activation. CSU maintains the appearance of hives or wheals which can continue for 6 weeks or more without any identifiable triggers.

“The barzolvolimab data reported today set a new bar for efficacy in CSU—demonstrating the highest rate of complete response observed in a well controlled study,” Martin Metz, MD, professor of dermatology and allergy at Charité - Universitätsmedizin in Berlin, said in a statement. "By addressing the root driver of chronic spontaneous urticaria, the mast cell, barzolvolimab provides early, durable and, most importantly, the opportunity for complete symptom control for the many patients who do not see meaningful benefit from the current standard of care…”

The drug itself is a humanized monoclonal antibody and designed to specifically target mast cells among patients by binding the receptor tyrosine kinase KIT with high specificity and potently inhibiting its activity. KIT is observed in many different cells, including mast cells, which play a crucial role in inflammatory responses such as allergic reactions and hypersensitivity.

For the purposes of assessing barzolvolimab’s safety and efficacy, the investigators conducted a randomized, placebo-controlled, double-blind, phase 2 analysis looking at several different dose regimens among individuals with CSU who also remain symptomatic despite antihistamine implementation.

There were 208 subjects in this study randomly assigned in a 1:1:1:1 ratio to be treated with either subcutaneous injections of barzolvolimab at doses of 75 mg every 4 weeks, 150 mg at the same every-4-week regimen, 300 mg at an every-8-week regimen, or a placebo over a 16-week timeframe.

After this period of the study, a 6-week active treatment phase was conducted, during which participants who had initially been given a placebo or 75 mg were adjusted to either be treated with 150 mg every 4 weeks or 300 every 8 weeks. Subjects who had already been on 150 mg or 300 mg continued with their same dosing regimen.

After the 52-week mark, the investigators switched subjects to a 24-week follow-up period. Overall, the team concluded that barzolvolimab met their primary efficacy goals, indicating a statistically significant improvement among patients in their weekly urticaria activity scores (UAS7) from baseline to the 12-week mark at all dose levels versus placebo.

Specifically, they found that 71% of subjects (150 mg Q4W) were successful in achieving a complete response at the 52-week mark.

The research team noted that the medication was well tolerated, adding that there had been a favorable safety profile over the course of the 52-week analysis. They highlighted that adverse events had predominantly been mild, associated with drug’s mechanism of action (KIT) and were believed to be reversible.

The investigators noted that among the study participants, the most common side effects, observed in over 10% of those given barzolvolimab, included skin hypopigmentation, shifts in hair color, neutropenia, urticaria, and nasopharyngitis. They added that these adverse events were not dependent on the dose which had been administered.

“Importantly, barzolvolimab was also well tolerated across the 52 week treatment period further supporting barzolvolimab’s significant potential to become a transformative treatment option for patients suffering from this often very severe and debilitating disease,” Metz said in his statement.

References

1. ^{Celldex Therapeutics Presents Landmark 52 Week Results from Barzolvolimab Phase 2 Study in Chronic Spontaneous Urticaria at EADV 2024. Celldex Therapeutics, Inc. https://www.globenewswire.com/en/news-release/2024/09/25/2953142/24180/en/Celldex-Therapeutics-Presents-Landmark-52-Week-Results-from-Barzolvolimab-Phase-2-Study-in-Chronic-Spontaneous-Urticaria-at-EADV-2024.html. September 25, 2024.}