Anti-KIT antibody: the next frontier in CSU treatment?

The 52-week results of a phase 2 trial showed promising results for barzolvolimab in treating chronic spontaneous urticaria (CSU), with up to three-quarters of participants reaching an Urticaria Activity Score over 7 days (UAS7) ≤6 after 1 year. The proportion of participants with fully controlled disease (i.e. UAS7=0) was not much lower.

“We need new therapies in this purely mast cell-driven disease because we still have many patients that are remaining symptomatic despite standard or up-dosed anti-histamine treatment, and despite omalizumab treatment,” Prof. Martin Metz (Charité-University Hospital Berlin, Germany) advocated [1]. The randomised-controlled phase 2 trial (NCT05368285) evaluates the humanised anti-KIT IgG1 monoclonal antibody barzolvolimab for the treatment of CSU and met its primary endpoint of mean change in UAS7 change from baseline at 12 weeks. Currently, Prof. Metz presented the 52-week results after a further 36 weeks of active treatment. For this extension, participants who previously received placebo or the 75 mg dose of barzolvolimab were re-randomised at week 16 to either 150 mg every 4 weeks or 300 mg every 8 weeks.

“We are really looking at very severely affected patients,” Prof. Metz commented on the baseline characteristics. The mean age was between 42.2 and 47.2 years, 71–80% of the participants were women, UAS7 score was 30.0–31.3, and around 20% had previous experience with omalizumab.

The previous 12-week results showed a significant drop of over 20 points in UAS7 in the 150 mg and 300 mg groups compared with 10.47 points on placebo (P<0.0001 for both comparisons) [2]. At week 52, well-controlled disease with a UAS7≤6 was achieved by 67.4–73.7% in the continuous barzolvolimab groups. Complete disease control (UAS7=0) was found in 52.3–71.1% [1]. “This is the best data for CSU that we have seen so far,” Prof. Metz highlighted. Stratification according to prior omalizumab treatment did not detect relevant differences in response.

“Most events that were seen were grade 1 and most importantly mechanism-related,” Prof. Metz detailed with special regard to KIT-mediated safety events like hair colour changes (26%), skin hypopigmentation (13%), and neutropenia (17%) after 52 weeks. Treatment-related serious adverse events occurred in 1%.

“Barzolvolimab has the potential to be an important new treatment option; phase 3 trials will give us more information on that,” Prof. Metz concluded.

1. 
   
   1. Metz M. Barzolvolimab shows profound efficacy and favourable safety over 52 weeks in patients with chronic spontaneous urticaria. D1T01.2D, EADV Congress 2024, 25–28 September, Amsterdam, the Netherlands.
   2. Maurer M, et al. J Allergy Clin. Immunol. 2024;153(2) Suppl. DOI: 10.1016/j.jaci.2023.11.873.

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Posted on 6 November 20246 November 2024