Chronic inducible urticaria improves in 12 weeks with barzolvolimab
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Key takeaways:
- Barzolvolimab is an anti-KIT monoclonal antibody.
- 75% of patients with cold urticaria and 66.5% of patients with symptomatic dermographism achieved partial or complete response.
BOSTON — Patients with chronic inducible urticaria saw improvements in itch and wheals with barzolvolimab in 12 weeks, according to an abstract presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
“There are currently no approved therapies for these conditions,” Jonathan A. Bernstein, MD, FAAAAI, FACAAI, FACP, adjunct professor of medicine at the University of Cincinnati College of Medicine, said during his presentation.
Barzolvolimab (CDX-0159, Celldex Therapeutics) is an anti-KIT monoclonal antibody. It “has demonstrated clinically meaningful and statistically significant improvement in itch and urticaria wheals accompanied by depletion of skin mast cells in chronic urticaria,” Bernstein said.
This phase 2, randomized, double-blind, dose-finding study compared the efficacy and safety of barzolvolimab with placebo among patients with cold induced urticaria (n = 96) or symptomatic dermographism (n = 97) that H1 antihistamines were unable to control.
Patients had been diagnosed with cold induced urticaria or symptomatic dermographism at least 3 months before the start of the study. They also had a positive provocation test at screening and an Urticaria Control Test (UCT) score of less than 12.
“Prior biologics were permitted,” Bernstein said.
Patients received 150 mg of barzolvolimab once every 4 weeks, 300 mg of barzolvolimab every 8 weeks or placebo every 4 weeks. The full analysis included 193 patients, and 173 patients (90%) completed 12 weeks of the study.
“Eight percent of patients treated with [barzolvolimab] discontinued treatment, compared with 14% of patients treated with placebo,” Bernstein said.
The demographics of the treatment and placebo groups were very similar, Bernstein continued. For example, mean ages in the cold urticaria group included 40 years for the 150 mg group (n = 32), 40 years for the 300 mg group (n = 32) and 41 years for the placebo group.
At week 12, percentages of patients with cold urticaria and negative provocation tests included 12.5% in the placebo group, 46.9% in the 150 mg group (P = .0023) and 53.1% in the 300 mg group (P = .0011).
Percentages of patients with symptomatic dermographism and a negative provocation test at week 12 included 3.2% in the placebo group, 57.6% in the 150 mg group (P < .0001) and 42.4% in the 300 mg group (P = .0003).
Additionally, in the cold urticaria group, 31.3% of the placebo group, 62.5% of the 150 mg group (P = .0118) and 75% of the 300 mg group (P = .0006) achieved complete or partial response.
Percentages of patients with complete or partial response in the symptomatic dermographism group included 12.9% of the placebo group, 66.6% of the 150 mg group (P < .0001) and 57.5% of the 300 mg group (P =.0002).
Bernstein classified these differences as statistically significant improvements.
“There was also marked improvement in critical threshold temperature and friction threshold to week 12,” Bernstein said.
Least square mean changes from baseline in critical temperature at week 12 among patients with cold urticaria group included –0.3°C for the placebo group, –8.82°C for the 150 mg group (P < .0001) and –9.61°C for the 300 mg group (P < .0001).
Least square mean changes from baseline in critical friction thresholds at week 12 among patients with symptomatic dermographism included –0.82 pins for the placebo group, –2.46 pins for the 150 mg group (P < .0001) and –2.27 pins for the 300 mg group (P = .0002).
Bernstein called these improvements in critical temperature and friction thresholds significant as well, with improvements seen as early as 2 weeks after the first dose and sustained through 12 weeks.
Improvements were seen as early as 2 weeks after the first dose in worst itch at the time of provocation testing as well, Bernstein continued. At 12 weeks, improvements were statistically significant for both doses in cold urticaria and symptomatic dermographism.
“There was greater or more pronounced response for cold induced urticaria,” Bernstein said.
Among patients with cold urticaria group, the 150 mg group (n = 29) included 58.6% with complete response, defined as a UCT score of 16, or well controlled response, defined as a UCT score of 12 or higher (P = .0048). The 300 mg patients in the cold urticaria group included 68.8% with complete or well-controlled response (P < .0001). The placebo patients included 31% with a complete or well-controlled response.
Percentages of patients with complete or well controlled response in the symptomatic dermographism group included 54.8% for the 150 mg group (n = 31; P = .0015), 65.5% for the 300 mg group (n = 29; P < .0001) and 32% for the placebo group (n = 25).
Bernstein called these improvements statistically significant as well.
“Ninety-eight percent of treatment-emergent adverse events were grade 1 or 2 and were 67% mild and 32% moderate,” Bernstein continued. “There were no differences in rates of discontinuation in the [adverse events] between active drug and placebo.”
Percentages of patients with any adverse event included 62% for the 150 mg group (n = 65), 60% for the 300 mg group, 61% for all patients treated with barzolvolimab (n = 130) and 52% for the placebo group. One patient in the 300 mg group experienced a treatment-related adverse event.
The most common events, changes in hair color and neutropenia, were related to the mechanism of the drug and expected to be reversible, Bernstein said.
“There was no association between infections and neutropenia, and events were mild and transient,” Bernstein said.
Bernstein called this work the first randomized single control study to demonstrate clinical benefits with barzolvolimab for patients with chronic inducible urticaria.
“The study met all primary and secondary endpoints at week 12, with significant and clinically meaningful improvements early with [barzolvolimab],” he said. “Phase 3 studies are currently planned.”
Bernstein also expressed surprise with these findings.
“I never thought I would be standing up here talking about a specific drug for inducible hives when I was a fellow,” he said.