Barzolvolimab Shows Prolonged Benefit in Chronic Spontaneous Urticaria, May Modify Disease Course

Patients with chronic spontaneous urticaria (CSU) experienced sustained positive outcomes weeks after completing treatment with barzolvolimab, a humanized monoclonal antibody targeting mast cells, according to data presented at the American Academy of Allergy, Asthma & Immunology (AAAI) Annual Meeting. These findings suggest barzolvolimab may not just alleviate symptoms but potentially modify the underlying disease process.

The research, led by Martin Metz, MD, head of translational research at Charité University Medicine, Berlin, and colleagues, indicates a durable effect extending beyond the treatment period.

Targeting the Root Cause of CSU

“Barzolvolimab is a humanized monoclonal antibody with a completely novel mechanism of action that uniquely targets the root cause of CSU — the mast cell,” explained Diane Young, MD, senior vice president and chief medical officer at Celldex Therapeutics.

Current CSU therapies often address individual inflammatory pathways or mast cell activation mechanisms. However, barzolvolimab directly targets mast cells, regardless of the specific pathways triggering their activation. This approach, Dr. Young noted, addresses the fundamental driver of CSU symptoms – chronic hives, itching, and angioedema.

“By addressing the root cause of the disease, barzolvolimab has demonstrated best-in-disease data in a robust, randomized placebo-controlled phase 2 study,” Dr. Young added.

Study Findings: Sustained Remission

In a phase 2 study, 93% of patients receiving barzolvolimab experienced a clinically meaningful response, with the highest rates of complete response – defined as a urticaria activity score over 7 days (UAS7) of 0 – observed in a clinical trial. At 12 weeks, 51% of patients receiving 150 mg of barzolvolimab every 4 weeks achieved complete response, increasing to 71% at 52 weeks.

Remarkably, the benefits persisted even after treatment cessation. Seven months after completing barzolvolimab treatment, 41% of patients maintained a complete response at Week 76. Improvements in angioedema control and quality of life were too substantial and sustained throughout the study period.

Exploratory Analysis: Disease Modification

An exploratory analysis focused on 48 patients who completed 52 weeks of treatment and had well-controlled disease at the end of the treatment period. At baseline, these patients had a mean UAS7 score of 31.1, indicating severe disease in 66.7% of the group. However, at week 52, 87.5% achieved a UAS7 score of 0 (complete response), and the remaining 12.5% had well-controlled urticaria.

Two weeks after the final dose, 50% of patients maintained complete response, and 18.8% had well-controlled disease. 69% of patients with well-controlled disease at week 52 continued to have well-controlled disease two weeks later, with 50% achieving complete response.

At week 76, half of the patients continued to have well-controlled disease, with a mean UAS7 score of 0.4 and a mean Dermatology Life Quality Index (DLQI) score of 1.17, with 83.3% scoring a 0 or 1 on the DLQI.

Implications and Future Research

These findings suggest barzolvolimab may modify the course of CSU for some patients. The majority of patients in the analysis (approximately 70%) had severe disease, including angioedema, reported poor quality of life at baseline, and had lived with CSU for a median of almost 6 years.

“The ability to be symptom free for an extended period of time off therapy is a tremendous benefit for patients and will be compelling for patients and physicians who may want to ‘take breaks’ in their therapy,” Dr. Young said.

Celldex Therapeutics is currently conducting global phase 3 trials, including EMBARQ-CSU1 and EMBARQ-CSU2, with a long-term extension to further evaluate response duration. The company is also investigating barzolvolimab in other mast cell-mediated conditions, including cold urticaria, symptomatic dermographism, prurigo nodularis, and atopic dermatitis.

Source: Metz M, et al. Poster 075. Prolonged off-treatment efficacy of barzolvolimab in chronic spontaneous urticaria. Presented at: AAAI Annual Meeting; Feb. 27-March 2, 2026; Philadelphia.

Disclosure: Young reports having employment with Celldex. Metz reports having financial relationships with AbbVie, ALK Abello, Almirall, Amgen, AstraZeneca, Celldex, Celltrion, Escient, Galderma, GSK, Novartis, Pfizer, Regeneron and Sanofi.