- Maurer M. The Bruton's tyrosine kinase inhibitor remibrutinib (LOU064) in chronic spontaneous urticaria: Top-line results of a phase 2b dose-finding study. D1T01.3C, EADV Congress 2021, 29 Sept–2 Oct.
The presented phase 2b study (NCT03926611) assessing remibrutinib as novel selective oral Bruton’s tyrosine kinase (BTK) inhibitor included 311 adult patients with CSU1. All participants suffered from CSU for at least 6 months, which was uncontrolled despite antihistamine treatment, and presented at baseline with an Urticaria Activity Score (UAS7) ≥16 points.
The dose-finding trial evaluated placebo versus 6 different dosages of remibrutinib, ranging from 10 mg once daily to 100 mg twice daily. The primary endpoint was defined as change from baseline UAS7 at week 4. Key secondary endpoints included UAS7 change at week 12, UAS7=0 response over time as well as safety and tolerability. “The key features and demographics were by and large evenly distributed,” stated Prof. Marcus Maurer (Charité University Hospital, Germany). The mean age was 45 years, 71.4% were women, 60.5% had severe CSU, and 56.9% had a history of prior angioedema. The mean duration of CSU was almost 5 years.
At the 4-week assessment, a clear dose-response relationship was present over the different study arms. “But more importantly, for all of these different doses used, we saw an effect with a marked reduction in disease activity measured by UAS7 as compared with placebo,” Prof. Maurer stressed. Looking at the changes over 12 weeks, there was an early onset of later maintained disease activity reduction in weeks 1 and 2 with least square mean changes in the different remibrutinib arms between -15.3 and -20.2 compared with -7.9 on placebo.
“Half of the patients who are treated with remibrutinib oral treatment achieve a marked reduction in their disease activity at the end, reflecting mild disease or well-controlled disease, so a very encouraging result for this oral BTK inhibitor,” Prof. Maurer further elaborated. In terms of safety, the drug was well-tolerated and showed no apparent dose-dependent adverse effects. “So, we will be very much looking forward to seeing remibrutinib developed for CSU and further studies to come our way,” summarised Prof. Maurer.