Rilzabrutinib for H1-antihistamines-refractrory CSU clears phase II trial

The BTK inhibitor rilzabrutinib helps lower disease activity in patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines, while having an acceptable adverse event (AE) profile, according to the results of the phase II RILECSU study.

RILECSU included 160 adult patients (mean age 44.1 years, 70.0 percent female) with weekly Urticaria Activity Score (UAS7) of at least 16 and weekly Itch Severity Score (ISS7) of at least 8, whose disease had not been adequately controlled with H1-antihistamine treatment. These patients were randomly assigned to receive rilzabrutinib 400 mg once every evening (400 mg/day), twice per day (800 mg/day), three times per day (1,200 mg/day), or matching placebo.

The primary endpoint was change in ISS7 (for US and US reference countries) or UAS7 (for non-US reference countries) at week 12. The primary analysis population included 143 omalizumab-naïve patients.

Compared with placebo, rilzabrutinib 1,200 mg/day was associated with significant reductions in ISS7 (mean, −9.21 vs −5.77; p=0.02) and UAS7 (mean, −16.89 vs −10.14; p=0.02). Improvements in weekly Hives Severity Score (HSS7) and weekly Angioedema Activity Score (AAS7) were also observed. All these changes occurred as early as week 1.

CSU-related biomarkers, such as soluble Mas-related G protein–coupled receptor X2, immunoglobulin (Ig)-G antithyroid peroxidase, IgG anti-Fc-ε receptor 1, and interleukin-31, decreased with rilzabrutinib vs placebo.

As for safety, rilzabrutinib showed a favourable risk-benefit profile. AEs including diarrhoea, nausea, and headache were more common with rilzabrutinib vs placebo.