Ligelizumab Demonstrates Superior Efficacy Over Xolair in Phase IIb Trial for Chronic Spontaneous Urticaria, Achieving 51% Complete Remission Rate

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Novartis recently announced that the results of the Phase IIb clinical trial (NCT02477332) evaluating the monoclonal antibody drug ligelizumab for the treatment of chronic spontaneous urticaria (CSU) have been published in the New England Journal of Medicine. The results showed that, in patients with chronic spontaneous urticaria whose condition was not adequately controlled by H1 antihistamines, ligelizumab demonstrated rapid onset of action and improved, sustained efficacy compared to Xolair.

This study was a multicenter, randomized, double-blind, placebo- and active-controlled, dose-finding trial conducted in patients with refractory chronic spontaneous urticaria (CSU) whose symptoms were inadequately controlled by H1 antihistamines. The aim was to evaluate the efficacy and safety of once-monthly subcutaneous ligelizumab as an add-on therapy. In the study, 382 patients were randomly assigned to receive either once-monthly subcutaneous ligelizumab (24 mg, 72 mg, or 240 mg), Xolair 300 mg, or placebo for 20 weeks, or a single dose of ligelizumab 120 mg.

During the study, disease symptoms such as wheals, pruritus, and angioedema were monitored using weekly activity scores. The primary objective of the study was to determine the dose-response relationship for complete resolution of urticaria. Complete resolution of urticaria was defined as a weekly Urticaria Severity Score of 0 (score range: 0–21), which also served as the primary endpoint, assessed at Week 12.

Data showed that at Week 12, complete resolution of urticaria was achieved in 30%, 51%, and 42% of patients treated with ligelizumab 24 mg, 72 mg, and 240 mg, respectively; the corresponding rate was 26% in the Xolair group and 0% in the placebo group.

A dose-response relationship was confirmed. At Week 12, complete symptom control was achieved in 30%, 44%, and 40% of patients receiving ligelizumab 24 mg, 72 mg, and 240 mg, respectively, compared with 26% in the Xolair group and 0% in the placebo group. The incidence of adverse events was similar across all study groups, and no safety concerns related to treatment with ligelizumab or Xolair were observed.

The above results indicate that, compared with patients receiving Xolair or placebo, the highest proportion of patients achieving complete control of chronic spontaneous urticaria symptoms was observed in those treated with 72 mg ligelizumab.

Chronic spontaneous urticaria is a dermatological condition characterized by the appearance of wheals, angioedema, or both in the absence of specific external triggers. It is a relapsing-remitting disorder of unknown etiology with a duration exceeding six weeks. Evidence indicates that the disease follows a prolonged course and negatively impacts quality of life. Although the pathogenesis of urticaria is not fully elucidated, autoimmune mechanisms are known to be involved in the majority of patients.

Currently, the disease is treated with second-generation antihistamines. When high-dose antihistamine therapy fails, anti-IgE monoclonal antibodies are usually added, with Xolair serving as a third-line treatment; nevertheless, many patients still fail to achieve complete symptom control.

Xolair is a monoclonal antibody drug that targets and binds to immunoglobulin E (IgE). Administered via subcutaneous injection, it likely works by reducing IgE levels and the downstream effects of cell activation mechanisms. Xolair was first approved in 2003 for the treatment of patients with asthma whose symptoms are difficult to control, and it received further approval in 2014 for patients with chronic urticaria refractory to H1 antihistamines. In China, Xolair was approved in August 2017 under the Chinese brand name Zhuole. It is also the first targeted therapy approved in China for the treatment of asthma.

In the United States, Xolair was co-developed and commercialized by Novartis and Genentech, achieving sales of $1.75 billion in the U.S. market in 2018. With a key patent for Xolair expiring last year, Novartis is actively advancing the clinical development of its successor product, ligelizumab.

Ligelizumab is a next-generation humanized anti-IgE monoclonal antibody that blocks the IgE/FcεR1 signaling pathway and exhibits higher IgE affinity than Xolair. Currently, ligelizumab is in Phase III clinical development.

Reference Source:

1、Novartis data show more patients are completely symptom-free from chronic spontaneous urticaria with ligelizumab (QGE031) thanXolair®300 mg

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3. The world’s first innovative targeted therapy for asthma, Xolair®, has been officially approved for launch in China