Prof. Margarida Gonçalo

Professor Marcus Maurer from The Charité urticaria team and the Urticaria Center of Reference and Excellence (UCARE) center in Berlin presented data from the PEARL-1 and PEARL-2 studies. These Phase 3 twin clinical trials studied the safety and efficacy of ligelizumab, a next-generation anti-IgE monoclonal antibody in the treatment of adult and adolescent patients with anti-H1 refractory chronic spontaneous urticaria (CSU). They were double-blind, placebo-controlled trials comparing two doses of ligelizumab (72 and 120mg) for 52 weeks, with the other anti-IgE – omalizumab – as a comparator. 

Ligelizumab has a very high affinity for IgE, which prevents its binding to the mast cell receptor – therefore hindering the mast cell stimulating effect of IgE against auto-antigens (TPO or IL-24) that are a relevant in autoallergic/Type I autoimmune CSU. Moreover, in the long term, as there is less IgE bound to mast cells, there is a progressive decrease of IgE receptors (FceRI) on mast cells, thereby reducing the target for pathogenic IgG antibodies anti-FceRI involved in Type IIb autoimmune urticaria.     

These studies involved about 2,000 patients, mostly females with a long disease duration (mean >4 years), a very high urticaria and angioedema activity scores (mean UAS7 >29; mean AAS around 20) and high impact on patient quality of life (mean DLQI >13), but with a similar distribution in the four arms (ligelizumab 72 mg, ligelizumab 120 mg, omalizumab 300 mg, or placebo subcutaneously every 4 weeks).

At 12 weeks, compared to placebo, there was a very significant UAS7 reduction in both ligelizumab doses (mean 20 points reduction in UAS7, which is twice the clinically meaningful difference for CSU improvement) and around 30% of patients achieved a complete CSU control (UAS7=0), but these data were not different from the omalizumab arm. There was no significant safety concern, except for a few more injection-site reactions and one possible anaphylactic reaction in the ligelizumab group.

As a whole, this new anti-IgE monoclonal antibody showed wonderful efficacy and safety results in CSU at 12 weeks, but these results were not different from omalizumab, the previous anti-IgE treatment which has been available for many years, and with which we are already very familiar. For the moment, no data were presented for the 52 weeks, and there were no evaluations in CSU subgroups. The results, although very promising, do not favor the replacement of omalizumab for ligelizumab in our clinical practice.