Barzolvolimab Showed Prolonged Clinical Efficacy in Chronic Hives

In this exclusive MedPage Today video, Jonathan Bernstein, MD, of the University of Cincinnati College of Medicine, discusses emerging data on barzolvolimab, an investigational humanized monoclonal antibody, in chronic spontaneous urticaria (CSU) presented at the American Academy of Allergy, Asthma & Immunology annual meeting.

Study outcomes showed evidence that some patients maintained disease control even after drug levels fell, suggesting the therapy may alter mast cell biology and potentially reshape the future treatment landscape.

Following is a transcript of his remarks:

This study, a double-blind placebo-controlled, patients who were refractory to antihistamines, H1 antihistamines, they were over a 52-week total treatment period, and then they went into a 24-week follow-up. So it’s a long study.

They did a post-hoc analysis of efficacy in patients during the 24-week follow-up who were randomized to receive the 150-[mg] every-4-week [dose] or the 300-[mg] every-8-week dose for 52 weeks. These patients all completed the full treatment period. They achieved at least well-controlled at week 52 — that was 55 patients — and had a reported UAS7 [weekly Urticaria Activity Score] at week 76 — so that’s 48 patients. So that’s who they included.

And so when you look at the figures, you can see that there’s different scores based on disease activity, different five distinct health states. Complete response was UAS7 0, well controlled is less than 8.6. Then mild disease was defined as 7-15 UAS7, and then moderate UAS7 was 16-27, and then severe disease 28-42.

And so when you look at the baseline UAS7 score, these patients had 32 as their baseline. So they had severe disease at baseline.

So over that period of time, week 52, only about 12.5% had well-controlled disease and over 87% had complete control. And over time, it seems to wane. Again, the study after the completion of the study, this is a 24-week follow-up, you can see that it was sustained, but then as you start getting out to week 66 and beyond, there are some people where the hives are starting to come back, and then more people are partially controlled rather than completely controlled.

So when you look at the concentration of barzolvolimab, you see that it falls below therapeutic windows by week 64, which corresponds to the changes that we’re seeing in disease control. And then you look at well-controlled disease, maintenance well-controlled disease, despite sub-therapeutic concentration.

So here’s barzo, you see the subconcentrations, and there’s a significant percentage of patients that still maintain; even though the barzo levels are very low, they still have some control.

So what they found was 50% of patients maintained UAS7, less people were sick throughout the follow-up period, and they had profound benefits on quality of life throughout the entire follow-up. And 83% reported a DLQI [Dermatology Life Quality Index] 0-1, which means no impact of the disease on quality of life at week 76.

So in conclusion, I think they were happy to say that the phase II trial of antihistamine-refractory CSU patients treated with barzo at different frequencies, whether it’s 150 [mg] every 4 [weeks] versus 300 [mg] every 8 [weeks] for 1 year, 70% had controlled disease at the end of the treatment period, and 88% had a complete control. And it induced prolonged clinical efficacy 7 months after the last dose.

So that’s always good to hear that one could actually back off on drug for a period of time and then potentially have to redose when symptoms start to come back later. But a 69% achieve well-controlled disease after 52 weeks of treatment and maintain it throughout the follow-up period, and 50% maintain complete disease control throughout the follow-up. And so there was sustained benefit of barzo and it correlated with barzo clearance and return of mast cells.

So it suggests that barzo does have disease modification abilities. And again, this just emphasizes that the potential value of this therapy, of this mechanism of action for treating chronic spontaneous urticaria in patients who are not well controlled on high dose antihistamines.

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