Antibody therapy keeps some with CSU swelling-free for months

The investigational therapy barzolvolimab rapidly reduced angioedema in people with chronic spontaneous urticaria (CSU) in a Phase 2 trial, and many remained free of swelling months after treatment ended.

At the trial’s final assessment, conducted at week 76 (about 17.5 months after the study began), as many as 64% of patients who had angioedema at the start of the study remained angioedema-free.

The findings suggest that barzolvolimab’s benefits may continue after dosing stops, developer Celldex Therapeutics said.

“Barzolvolimab has consistently shown profound, lasting results including high rates of complete response, defined as complete absence of itch and hives, and dramatic improvements in quality of life and angioedema control through 52 weeks of therapy and now seven months after the last dose, demonstrating its potential for disease modification and the ability to change how CSU patients live their lives,” Diane C. Young, MD, senior vice president and chief medical officer of Celldex, said in a company press release.

The results were described at the European Academy of Allergy and Clinical Immunology’s (EAACI) annual meeting in Istanbul, Turkey, in a presentation titled, “Long-Term Barzolvolimab Treatment Results in Sustained Off-Treatment Improvement in Angioedema in Patients With Chronic Spontaneous Urticaria Refractory to Antihistamines.”

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Angioedema has ‘major role’ in quality of life

CSU is a chronic, inflammatory condition characterized by recurring hives and itching that appear without a known trigger and persist for at least six weeks. Angioedema, a form of swelling in the deeper layers of the skin or mucus membranes, affects about half of people with CSU and is associated with more severe, longer-lasting disease and poorer quality of life.

“Angioedema plays a major role in the physical and mental health of the majority of people living with CSU, causing extremely painful swelling and disfigurement that dramatically impacts quality of life,” said Young.

People with CSU-related angioedema may experience worse physical and mental health, greater difficulty working or performing daily activities, and more emergency room visits and hospitalizations than those without angioedema.

CSU is largely driven by mast cells, immune cells that release histamine and other inflammatory substances involved in itching, hives, and swelling.

Treatment commonly begins with antihistamines, but symptoms persist for some people despite these medications.

Barzolvolimab is an experimental antibody that blocks KIT, a protein required for mast cell survival and activity. Blocking KIT is intended to reduce the number and activity of mast cells, which contribute to CSU symptoms.

The Phase 2 trial (NCT05368285) evaluated adults with moderate to severe CSU that remained active despite antihistamine treatment. The analysis presented at EAACI covered 207 participants who were randomly assigned to receive under-the-skin injections of barzolvolimab at 75 mg every four weeks, 150 mg every four weeks, or 300 mg every eight weeks. A fourth group received a placebo every four weeks.

The placebo-controlled part of the study lasted four months, followed by a little over eight months of active treatment and 24 weeks of follow-up. In the active treatment part of the trial, those initially assigned to the placebo or the 75 mg dose were reassigned to receive barzolvolimab at either 150 mg every four weeks or 300 mg every eight weeks. Those already receiving either of the higher doses continued their assigned treatment.

Of the 207 participants, 149 (72%) had angioedema at the start of the study. Their average weekly Angioedema Activity Score (AAS7) ranged from 53 to 56 points across groups, indicating severe angioedema symptoms. The AAS7 assesses five aspects of angioedema: how long the swelling lasts, physical discomfort, its effects on daily activities and appearance, and overall severity. Scores range from 0 to 105, with higher scores indicating more severe symptoms.

Participants with angioedema at the study’s start also tended to have lived with CSU for longer and had poorer quality of life than those without angioedema.

Reductions in angioedema scores were observed as early as the first week among participants initially treated with 150 mg every four weeks or 300 mg every eight weeks. Some participants in these groups became angioedema-free by the second week of treatment.

Those who initially received a placebo or the lowest barzolvolimab dose experienced further rapid improvements after switching to a higher-dose regimen.

At week 52, average AAS7 reductions ranged from 39.82 to 47.75 points across the four original treatment groups. Between 67% and 77% of participants who had angioedema when the trial began were free of swelling at that point.

The improvements continued after treatment ended. At week 76, up to 28 weeks after the last dose, average AAS7 scores remained 31.52 to 43.11 points below their starting levels. Between 52% and 64% of participants across the four original groups also remained angioedema-free.

Celldex said the continued benefits after treatment withdrawal suggest that barzolvolimab may have the potential to modify the disease rather than only control symptoms. However, this possibility will require confirmation in larger, longer-term studies.

Two Phase 3 trials, EMBARQ-CSU1 (NCT06445023) and EMBARQ-CSU2 (NCT06455202), are evaluating barzolvolimab in people with CSU that is not adequately controlled by antihistamines.

Both trials have completed enrollment. Together, they enrolled 1,939 participants across more than 500 sites in 43 countries, including people who had previously received advanced therapies or whose disease did not respond adequately to them.

Top-line results are expected later this year. Celldex plans to use the data to support an application seeking regulatory approval for barzolvolimab in 2027.