Among antihistamine-refractory patients with chronic spontaneous urticaria (CSU) who had at least well-controlled disease after a year of treatment with barzolvolimab, a novel humanized monoclonal antibody, more than two-thirds remained well controlled 7 months after the last dose, according to data from a phase 2, dose-finding study presented at the AAAAI meeting.
Half of patients maintained a complete response, defined as a weekly Urticaria Activity Score (UAS7) of 0, with these sustained effects observed despite diminishing concentrations of barzolvolimab and an increase in mast cell numbers after treatment ended.
The analysis suggests that barzolvolimab may lead to disease modification in CSU and “indicates that we might not need to treat patients for years but could possibly treat them for 12 months (or maybe shorter?) and then stop treatment,” Martin Metz, MD, deputy director of the Institute of Allergology at Charité-Universitätsmedizin Berlin, Germany, told Doximity via email, adding that “eventually, treatment would need to be reinitiated after return of symptoms.”
In the phase 2 study, patients with antihistamine-refractory CSU were initially randomized to subcutaneous injections of barzolvolimab at doses of 75 or 150 mg every 4 weeks or 300 mg every 8 weeks, or placebo every 4 weeks, for a period of 16 weeks. Patients who received the 75-mg dose or placebo were then re-randomized to one of the two higher doses of barzolvolimab for another 36 weeks, with those already receiving a dose of 150 or 300 mg maintaining those regimens. All patients were treated for a total of 1 year.
Previously reported results showed that barzolvolimab induced a clinically meaningful improvement in UAS7 by 12 weeks, with an even greater response observed by 52 weeks. Up to 74% of patients at that time point had well-controlled disease, defined as a UAS7 ≤6.
The current post-hoc analysis examined what happened after 1 year in the 48 patients (mean age 47.5 years; 72.9% women) who achieved well-controlled disease by the end of treatment and had a UAS7 available after an additional 24 weeks of follow-up (ie, at week 76), which is about 7 months after the last dose of barzolvolimab was administered.
By week 76, 50% of those patients had a complete response and 19% had well-controlled disease, even though the concentration of barzolvolimab dropped below the therapeutic level by week 64. In addition, levels of circulating tryptase indicated that there were normal numbers of mast cells by week 76, though “they did not reach the slightly elevated levels identified at baseline,” Metz said.
Gains in quality of life according to the Dermatology Life Quality Index (DLQI) were sustained through week 76 as well, particularly among those who maintained a UAS7 ≤6 for the entire follow-up period. In fact, 83% of this group had a DLQI of 0 or 1 at the end of the study, indicating that the disease had no effect on their lives.
Metz said the exact mechanism underlying barzolvolimab’s lasting off-treatment effects is unclear, noting that phase 3 trials—EMBARQ-CSU1 and EMBARQ-CSU2—will provide additional insights.
“We also have to get information on the cytokine milieu in the skin after long-term barzolvolimab treatment, as well as information on actual skin mast cell number in the skin of these patients,” he said.
Todd Neale has no conflicts of interest to report.
Illustration by Jennifer Bogartz
