Celldex Reports Strong Efficacy of Barzolvolimab in Chronic Spontaneous Urticaria Across IgE Subgroups

Celldex Therapeutics recently announced new data showing that barzolvolimab demonstrated rapid and sustained efficacy in patients with chronic spontaneous urticaria (CSU), regardless of baseline immunoglobulin E (IgE) levels. The results were presented in an oral e-poster session at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France.¹

Across both IgE subgroups (< 40 and > 40), barzolvolimab achieved comparable improvements in weekly Urticaria Activity Scores (UAS7), with consistent mean changes from baseline at weeks 12 and 52. Rates of well-controlled disease (UAS7 < 6) and complete disease control (UAS7 = 0) were similar in both subgroups. Comparable outcomes were also observed with Urticaria Control Test (UCT7) assessments, including well-controlled disease (UCT7 > 12) and complete disease control (UCT7 = 16) at weeks 12 and 52.

The findings build on earlier phase 2 trial results, in which barzolvolimab met its primary end point of significant UAS7 improvement vs placebo at 12 weeks across all dose groups. Complete response rates (UAS7 = 0; no itch/no hives) were observed in up to 51% of patients by week 12, increasing to 71% after 52 weeks of active therapy. Notably, sustained benefit persisted well beyond dosing: At week 76, up to 41% of patients maintained a complete response, and 48% reported no quality-of-life impact from CSU.

“These data reinforce that mast cells are important drivers of CSU and that barzolvolimab, with its novel mechanism of action, has significant potential to be a meaningful treatment for all patients with CSU, regardless of underlying disease endotype,” Diane C. Young, MD, senior vice president and chief medical officer of Celldex, said in the news release. “This is especially important for patients with low IgE levels, who typically have more severe disease and are less likely to respond to IgE-targeted therapies, including omalizumab.”

Barzolvolimab was well tolerated, with a favorable safety profile across treatment durations. No new safety concerns emerged during the study.

Celldex is now advancing barzolvolimab into phase 3 evaluation through the global EMBARQ-CSU1 (NCT06445023) and EMBARQ-CSU2 (NCT06455202) trials, enrolling patients with CSU who remain symptomatic despite H1 antihistamine therapy, including those who previously failed biologics.

Barzolvolimab, a humanized monoclonal antibody targeting KIT, represents a novel approach in CSU management by directly inhibiting mast cell function and survival. The investigational agent is also being studied in cold urticaria, symptomatic dermographism, prurigo nodularis, and atopic dermatitis.

In May 2025, a study published in the European Journal of Allergy and Clinical Immunology reported high percentages of patients achieving well-controlled and complete responses after treatment with barzolvolimab vs placebo. Overall, barzolvolimab demonstrated rapid symptom reduction in adult patients with moderate to severe antihistamine-refractory CSU.²

Researchers conducted a phase 1b, double-blinded, randomized study (NCT04538794) evaluating the safety, pharmacokinetics, and pharmacodynamics of barzolvolimab. Participants were assigned to receive barzolvolimab or placebo on 1 of 2 dosing schedules (ie, every 4 or 8 weeks). The study included a 2-week screening phase, 12 weeks of treatment, and a 12-week follow-up.²

Barzolvolimab demonstrated robust and sustained suppression of serum tryptase. Within days of the initial dose, tryptase levels dropped by more than 90% in the 1.5-mg/kg and higher-dose cohorts and remained suppressed throughout the 12-week dosing period.²

Clinically meaningful reductions in disease severity were observed in barzolvolimab-treated patients across all cohorts. By week 12, average UAS7 scores declined substantially, with the 3.0-mg/kg and 4.5-mg/kg groups experiencing reductions of 30 to 35 points compared with baseline. In contrast, placebo-treated patients showed minimal change.²

References

1. Celldex presents data demonstrating barzolvolimab improves chronic spontaneous urticaria independent of baseline immunoglobulin E levels in phase 2 study at EADV Congress 2025. News release. BioSpace. September 17, 2025. Accessed September 17, 2025. https://www.biospace.com/press-releases/celldex-presents-data-demonstrating-barzolvolimab-improves-chronic-spontaneous-urticaria-independent-of-baseline-immunoglobulin-e-levels-in-phase-2-study-at-eadv-congress-2025
2. Maurer M, Metz M, Anderson J, et al. Anti-KIT barzolvolimab for chronic spontaneous urticaria. Eur J Allergy Clin Immunol. Published online May 26, 2025. doi:10.1111/all.16598