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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 , 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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