Among patients with chronic spontaneous urticaria (CSU) who achieved a complete response after 1 year of treatment with barzolvolimab, half met the criteria for a complete response 7 months after receiving the last dose, in a study presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 Annual Meeting.

Barzolvolimab, a humanized monoclonal antibody, works by targeting mast cells through binding with the KIT receptors (a tyrosine kinase receptor involved in blood cell development) and inhibiting their activation.

In a subanalysis of patients enrolled in a phase 2 study, researchers examined posttreatment efficacy in patients who were well controlled after 52 weeks. The study population included 78 adults with antihistamine-refractory CSU aged 18-75 years who were treated with barzolvolimab at doses of 150 mg every 4 weeks or 300 mg every 8 weeks and who completed 52 weeks of treatment. Well-controlled disease was defined as urticaria activity scores of 6 or less over 7 days (UAS7 ≤ 6) at 52 weeks, and 55 (70.5%) met this endpoint at that time. In the exploratory analysis, the researchers examined data from 48 patients with UAS7 < 6 scores at week 52 and UAS7 scores available at 76 weeks.

Of these patients, 70.9% had severe disease at baseline. At 52 weeks, 87.3% had a complete response (UAS7 of 0), and the remaining 12.7% had well-controlled urticaria. The investigators, led by Martin Metz, MD, professor in the Department of Dermatology and Allergy and head of translational research at Charité-Universitätsmedizin in Berlin, Germany, reported that 28 weeks after receiving their final dose, “at least mild disease” was apparent in 81% of patients, 50% had a complete response, and 18.8% had well-controlled disease.

Patients maintained their improvements off treatment, even after clearance of barzolvolimab and normalization of serum tryptase, a mast cell biomarker, they said. At 76 weeks, disease was still well controlled in half of these patients, with a mean UAS7 score of 0.4, a mean score on the Dermatology Life Quality Index (DLQI) of 1.17, and a DLQI of 0 or 1 — meaning no impact of disease on their quality of life — in 83.3%.

Expanding Options

Studies of barzolvolimab are important because of the need for more effective drugs to treat CSU, said Allen P. Kaplan, MD, clinical professor of medicine at the Medical University of South Carolina, Charleston, South Carolina.

“There are patients unresponsive to antihistamines and omalizumab who need alternatives to cyclosporine because of the side effects one can encounter,” said Kaplan, who was not involved in the current study but has consulted for the manufacturer Celldex on barzolvolimab research.

In the current study, the high response rate to barzolvolimab was not surprising, but the surprising finding was the long-term remissions reported in some patients after the drug was stopped, Kaplan noted. “We need more data of this sort to be sure,” he said.

Potential barriers to the clinical use of barzolvolimab include the streaking-like hair color changes seen in some patients, although these are reversible, Kaplan told Medscape Medical News. However, “the drug works by depleting mast cells in the skin, which is a unique mechanism that might have broad utility in many inflammatory skin diseases,” he added.

Overall, the efficacy for patients with severe CSU was very good, so once approved, barzolvolimab will compete with currently approved CSU treatments remibrutinib and dupilumab, he said.

The findings were limited by the small sample size, the researchers noted. However, enrollment has been completed for two phase 3 studies, including a total of 1939 patients with CSU, according to a press release from Celldex.

More data are expected to be available in the fourth quarter of 2026, with a Biologics License Application planned for 2027, according to the company.

The study was funded by Celldex. Several authors reported being employees of Celldex. Kaplan disclosed consulting work for Celldex outside of the current study.