**10. Anti-IgE therapeutics under development**

#### **10.1 Ligelizumab**

Ligelizumab (QGE031) is a new promising humanizaed monoclonal anti-IgE antibody under development for the treatment of CSU patients. It has a 40-fold to 50-fold greater affinity to IgE compared with omalizumab [54]. In a phase 2b multicenter randomized placebo controlled trial, patients with antihistamine-refractory CSU were randomized to placebo, 300 mg of omalizumab, or 24, 72, or 240 mg of ligelizumab administered by subcutaneous injection with 4-week interval for 20 weeks [55]. Ligelizumab demonstrated rapid onset of action, dose-dependent efficacy, and superiority to omalizumab. At 12 week, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg of ligelizumab, respectivity, had complete control of urticaria, as compared with 26% of the patients receiving omalizumab 300 mg and none in the placebo group. More than 50% of patients taking 240 mg of ligelizumab were complete responders, a response rate twice than that seen in the omalizumab group. Furthermore, the mean time to relapse after the last injection was 4 weeks for omalizumab vs. 10 weeks for ligelizumab. Except higher rates of mild injection site reactions in the 240 mg of ligelizumab group, no difference in safety profiles of placebo, omalizumab, and ligelizumab was observed. The most frequently reported adverse events were viral upper respiratory tract infection and headache. No deaths or anaphylaxis events were reported in any of the trial groups. On the basis of favorable response of ligelizumab with a rapid onset of action, improved and sustained efficacy in antihistamine-refractory CSU patients over 300 mg of omalizumab treatment, now two phase III, multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group studies (PEARL 1 and 2) are running. The primary outcome of these two trials will measure absolute change from baseline in UAS7 at Week 12 [56].

#### **10.2 Quilizumab**

Quilizumab, a humanized, afucosylated, monoclonal IgG1 antibody, binds membrane IgE at the M1-prime segment, which is absent in soluble IgE. In animal studies, quilizumab bound membrane IgE on IgE-switched B cells and plasmablasts and depleted them through apoptosis and antibody-dependent cell-mediated cytotoxicity [57]. In clinical trials, quilizumab reduced serum total and specific IgE levels in healthy volunteers and in patients with allergic rhinitis or mild asthma [58]. However, because quilizumab did not provide a significant differences in the clinical endpoints compared with placebo, it was indicated that ongoing IgE switching and stimulation of B-cell memory may not be key disease drivers [59].
