BACKGROUND:Chronic urticaria (CU) is a debilitating mast cell-driven disease, often refractory to standard therapy (i.e., antihistamines). Lirentelimab, an anti-Siglec-8 monoclonal antibody, selectively inhibits mast cells and depletes eosinophils.
OBJECTIVE:Determine safety and efficacy of lirentelimab in patients with chronic urticaria.
METHODS:This phase 2a study enrolled CU patients refractory to up to four-fold H1-antihistamine doses. Patients received six monthly intravenous doses of lirentelimab (0.3, 1 and up to 3mg/kg). Primary efficacy endpoint was change in urticaria control test (UCT) score at week 22. Urticaria activity score (UAS7) was assessed in patients with chronic spontaneous urticaria (CSU) and CholUAS7 was used for cholinergic urticaria (CholU) patients.
RESULTS:45 patients were enrolled in 4 cohorts (n=13 omalizumab-naïve CSU, n=11 omalizumab-refractory CSU, n=11 cholinergic urticaria [CholU], n=10 symptomatic dermographism [SDerm]). UCT scores increased with lirentelimab across cohorts, with mean changes at week 22 of 11.1±4.1, 4.8±7.0, 6.5±6.2, and 3.4±4.1 and complete response rates (UCT ≥12) of 92%, 36%, 82%, and 40%, respectively. In omalizumab-naïve and -refractory CSU patients, disease activity decreased at week 22 (mean UAS7 change: -73% and -47%, respectively), with UAS7 response rates (≥50% reduction) of 77% and 45%, respectively. In SDerm patients, 50% (5/10) and 40% (4/10) had complete itch and hive resolution by FricTest, respectively, and 100% (7/7) evaluable CholU patients had negative responses to pulse-controlled ergometry exercise test. Most common adverse events included infusion-related reactions (43%; all mild/moderate and transient), nasopharyngitis (21%), and headache (19%). No treatment-related serious adverse events occurred.
CONCLUSION:Lirentelimab demonstrated activity across three forms of antihistamine-refractory CU.