WASHINGTON — Barzolvolimab, a first-in-class anti-KIT monoclonal antibody, reduced the severity of hives in adults with chronic spontaneous urticaria (CSU) who remained symptomatic on antihistamines, a randomized phase II trial showed.
Compared with placebo, several doses of the investigational drug produced greater improvement in the 7-day Urticaria Activity Score (UAS7) from baseline to week 12:
- Placebo every 4 weeks: least squares mean change -10.47
- 75 mg every 4 weeks: -17.06 (P=0.0017)
- 150 mg every 4 weeks: -23.02 (P<0.0001)
- 300 mg every 8 weeks: -23.87 (P<0.0001)
The changes observed on the UAS7 — 0 to 42 scale where higher scores indicate worse severity — began early, according to Marcus Maurer, MD, of the Charité-Universitätsmedizin Berlin, who presented the findings at the American Academy of Allergy, Asthma & Immunology annual meeting.
“What’s exciting, on top of the high treatment efficacy that we see 12 weeks into the treatment, is how fast this works,” said Maurer. “Within the first 2 weeks of treatment, you have patients experiencing significant benefit with all three doses but most pronounced with the highest dose.”
In terms of secondary endpoints — 7-day Hives Severity Score (HSS7) and Itch Severity Score (ISS7) — barzolvolimab also yielded clinically and statistically significant improvements in the trial. Furthermore, benefits in UAS7 were comparable whether patients were naive or experienced/refractory to omalizumab (Xolair), a biologic approved for CSU patients who remain symptomatic despite the use of antihistamines.
CSU is characterized by intense itching caused by wheals or hives without a clearly distinguishable trigger. The disease is driven by mast cells, said Maurer, which rely on KIT receptors for activation, tissue recruitment, and survival. In prior studies, the anti-KIT monoclonal antibody barzolvolimab (or CDX-0159) demonstrated the ability to deplete skin mast cells in urticaria while reducing itch and lesion severity.
Disease control was significantly better among patients receiving barzolvolimab, said Maurer. Well-controlled disease status (a UAS7 score of 6 or less), was achieved by 41.7% of those who received the 75-mg dose of barzolvolimab, 59.6% of the 150-mg group, and 62.5% of the 300-mg group, compared with 12.8% of placebo patients.
“Maybe more important than the average reduction in disease activity to patients is, ‘What is my chance when I use this treatment, of achieving the treatment goal?'” said Maurer. “The treatment goal is to treat the disease until it is gone — that’s what we say in the guideline. Gone is gone. No more wheals, no more itch, no more angioedema.”
To that end, complete responses — a UAS7 score of 0 — were achieved by 23% of the 75-mg group, 51.1% of the 150-mg group, 37.5% of the 300-mg group, and 6.4% of placebo patients.
Adverse event rates ranged from 53-61% across the various doses of barzolvolimab, compared with 28% with placebo. Among the most common adverse events were skin and subcutaneous tissue disorders and infections and infestations. One patient in the 300-mg barzolvolimab cohort experienced a serious adverse event, which was deemed unrelated to treatment. Some patients in the intervention groups also experienced nervous system disorders, hair color changes, and neutropenia — events not observed in the placebo group.
In order to be included in the phase II study, adult patients with CSU needed to have their diagnosis for at least 6 months, have itching and hives for 6 consecutive weeks or more despite using a second generation antihistamine, and be refractory to a stable second-generation antihistamine regimen. Patients also needed to have UAS7 scores of 16 or above and ISS7 scores of 8 or higher.
Those with other skin conditions resulting in hives or angioedema were excluded from the trial, as were those with other reasons for chronic itching and people with chronic urticaria with a clear sole or prominent trigger for symptoms.
A total of 207 participants were ultimately included in the study and randomized 1:1:1:1 to either the three barzolvolimab doses or placebo, with all administered subcutaneously. Across groups, the average patient age ranged from 42-47 years, and three-fourths were women, with 78% white, 14% Black, and 10% Asian.
At baseline, UAS7 and Urticaria Control Test scores were fairly similar between the cohorts, being in the range of 30.1-31.3 and 2.96-3.74, respectively. Patients had their CSU for over 5 years on average. More than 70% of the patients had angioedema at baseline and about 20% had previously been treated with omalizumab.
After 16 weeks, all patients on the 75-mg dose and placebo will be re-randomized to receive either the 150-mg or 300-mg doses of barzolvolimab for 20 more weeks.
Maurer noted that phase III studies of barzolvolimab are planned to begin this year.
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Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow
Disclosures
This study was sponsored by Celldex Therapeutics.
Maurer reported relationships with Allakos, Alvotech, Amgen, Aralez, AstraZeneca, Bayer, Celldex, Celltrion, Evommune, GSK, Ipsen, Kashiv, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Mitsubishi Tanabe Pharma, Moxie, Noucor, Novartis, Orion Biotechnology, Resonance Medicine, Sanofi/Regeneron, Septerna, Trial Form Support International AB, Third Harmonic Bio, ValenzaBio, Yuhan Corporation, and Zura Bio.
Primary Source
American Academy of Allergy, Asthma & Immunology
Source Reference: Maurer M, et al “Barzolvolimab significantly decreases chronic spontaneous urticaria disease activity and is well tolerated: top line results from a phase 2 trial” AAAAI 2024; Abstract L18.
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