Ligelizumab, a next-generation anti-IgE antibody, is safe and effective in treating patients with H1-antihistamine (H1-AH) refractory chronic spontaneous urticaria (CSU), according to two phase III studies presented at EADV 2022.
The pooled PEARL 1 and 2* cohorts consisted of 2,057 patients (mean age 42.8 years, 71.9 percent female) with CSU refractory to H1-AH. Of these, 62.5 percent had severe CSU and 35.3 percent had moderate CSU for a mean duration of 4.8 years. Participants were randomized to receive ligelizumab 72 mg (n=614) or 120 mg (n=616), omalizumab 300 mg (n=618), or placebo (n=209) subcutaneously every 4 weeks for up to 52 weeks. At week 24, all placebo recipients were switched over to ligelizumab 120 mg. [EADV 2022, abstract 3590]
At 12 weeks of follow-up, patients who received either dose of ligelizumab had significantly greater reductions in weekly Urticaria Activity Score (UAS7) than those who received placebo (least squares [LS] mean change from baseline, -19.3 [72 mg] and -19.8 [120 mg] vs -10.3; one-sided p<0.0001 for both doses).
In addition, more patients on ligelizumab achieved UAS7=0 (complete response), indicating no wheals and itch for 7 days, than those on placebo at week 12 (31.0 percent [72 mg] and 33.8 percent [120 mg] vs 5.7 percent).
Both ligelizumab- and omalizumab-treated patients showed similar reductions in UAS7 (LS mean change from baseline -19.3 [72 mg] and -19.8 [120 mg] vs -19.8 [omalizumab]). The proportion of patients achieving complete response was also similar between the ligelizumab and omalizumab groups (31.0 percent [72 mg] and 33.8 percent [120 mg] vs 34.1 percent [omalizumab]).
However, a slightly higher rate of injection site reactions was observed in the ligelizumab group than the omalizumab group (9.4 percent [72 mg] and 11.1 percent [120 mg] vs 3.8 percent [omalizumab]). Despite this, no new safety concerns were observed.
Ligelizumab was a “very safe and well-tolerated” treatment for CSU, said lead author Professor Marcus Maurer from the Institute of Allergology at Charité - Universitätsmedizin Berlin in Berlin, Germany.
“The primary endpoint of the ligelizumab phase III studies, PEARL 1 and PEARL 2, was met in terms of superiority of ligelizumab over placebo; however, superiority to omalizumab was not demonstrated,” Maurer said.
“[Nevertheless,] ligelizumab exhibited a good efficacy profile on urticaria activity in patients with moderate-to-severe CSU,” he added.
*PEARL 1 and 2: A phase III study of efficacy and safety of ligelizumab in the treatment of CSU in adolescents and adults inadequately controlled with H1-antihistamines