Novartis Announces Mechanistic Study Supporting Superior Efficacy of Ligelizumab Over Xolair in Chronic Spontaneous Urticaria

Novartis recently announced the results of a mechanistic study demonstrating that ligelizumab (QGE03) is more effective than the company’s marketed drug Xolair (omalizumab) in inhibiting the key pathogenic IgE/FcεRI pathway in chronic spontaneous urticaria (CSU).

Data show that ligelizumab binds to IgE with an affinity 88 times greater than that of Xolair. Furthermore, ligelizumab and Xolair differ in their recognition and binding epitopes on IgE, resulting in significantly enhanced blockade of IgE/FcεRI signaling by ligelizumab. This mechanistic study represents a major advance in understanding how different anti-IgE therapies exhibit distinct inhibitory characteristics both qualitatively and functionally.

Previously reported Phase IIb study results showed that a higher proportion of patients with chronic spontaneous urticaria (CSU) achieved complete resolution of symptoms with ligelizumab compared to Xolair. This mechanistic study further supports these findings, indicating that ligelizumab has the potential to transform the treatment landscape for CSU and may offer a superior therapeutic option for patients with this condition.

Chronic spontaneous urticaria (CSU) is a dermatological condition characterized by the appearance of wheals, angioedema, or both in the absence of specific external triggers. It is an idiopathic, relapsing-remitting disease with a duration exceeding six weeks. Evidence indicates that the prolonged course of this condition negatively impacts quality of life.

Xolair is a monoclonal antibody drug that targets and binds to IgE, administered via subcutaneous injection. The drug was first approved in 2003 for the treatment of patients with asthma whose symptoms are difficult to control, and it was approved again in 2014 for chronic spontaneous urticaria (CSU) refractory to H1 antihistamines.

Xolair was co-developed and co-promoted by Novartis and Genentech, a subsidiary of Roche. In the first nine months of 2019, the drug generated sales of $870 million for Novartis and $1.49 billion for Roche. With patent protection for Xolair having expired in the United States and Europe, Novartis is currently actively advancing the clinical development of ligelizumab.

Ligelizumab is a next-generation humanized anti-IgE monoclonal antibody that blocks the IgE/FcεRI signaling pathway and exhibits higher IgE affinity than Xolair. Currently, ligelizumab is in Phase III clinical development for the treatment of patients with chronic spontaneous urticaria (CSU) who are inadequately controlled by H1 antihistamine therapy. The Phase III program comprises two Phase III clinical studies (PEARL 1 and PEARL 2), which have enrolled more than 2,000 patients across 48 countries worldwide.

According to the U.S. clinical trials database ClinicalTrials.gov, data from these two Phase III studies will be released later this year, with study completion scheduled for 2021. If all goes well, Novartis will submit a marketing application for ligelizumab by the end of 2021.

As a successor to Xolair, if ligelizumab successfully reaches the market, it will help Novartis defend its franchise in the treatment of chronic spontaneous urticaria (CSU).

Reference Source: Novartis reveals positive efficacy data for Xolair follow-up

Original Title: Novartis Announces Mechanism Study Results, Supporting Ligelizumab’s Superior Efficacy Over Xolair in Treating CSU!