Ligelizumab for the treatment of chronic spontaneous urticaria

ABSTRACT

Introduction

Due to daily hives with itch, sleeplessness, and unforeseen development of angioedema, chronic spontaneous urticaria significantly impairs quality of life, often for years. Its management is challenging. In most cases, H1-antihistamines are not effective. Although the disease is not characterized by specific IgE antibodies against allergens, the last decade demonstrated that neutralizing IgE by using the monoclonal anti-IgE antibody Omalizumab is safe and effective. Nevertheless, symptoms are not controlled by Omalizumab in approximately one-fourth of patients.

Areas covered

This review is focused on Ligelizumab (QGE031), a next-generation non-triggering fully human monoclonal antibody, with higher affinity to IgE compared to Omalizumab.

Expert opinion

In chronic spontaneous urticaria, subcutaneous Ligelizumab once per month for five months has shown a clear dose–response relationship with respect to symptoms. Superiority over Omalizumab was noted whereas the safety profile was similar. Most common side effects were injection site reactions. In the near future, results from phase 3 trials, two of them including more than 1000 patients each, are awaited. Having a higher affinity to IgE and being more effective than Omalizumab, Ligelizumab has the potential to free chronic urticaria patients from year-long daily annoying symptoms that did not respond to standard therapy as recommended by current guidelines.

KEYWORDS:

• Anti-IgE therapy
• Ligelizumab
• monoclonal antibody
• Omalizumab
• urticaria

Article highlights

• Chronic spontaneous urticaria is a common, challenging, long-persisting, and annoying disease characterized by daily or nearly daily itching hives and/or angioedema.

• Recent years demonstrated that the interaction of IgE with the high-affinity IgE receptor (FcεRI) plays a crucial pathogenic role. IgE antibodies are not directed against common allergens but against an array of autoantigens (Type I autoimmunity). There is additional evidence for the role of IgG autoantibodies (Type IIb autoimmunity).

• Approval of monoclonal anti-IgE therapy with Omalizumab in 2014 represented a milestone in the treatment of H1-antihistamine refractory patients but is not sufficient in about one-fourth of the patients.

• Ligelizumab (QGE031) represents a next-generation monoclonal anti-IgE antibody with higher affinity to IgE compared to Omalizumab, and first published phase IIb study results demonstrated superiority over omalizumab while the good safety profile was comparable.

• In the near future, results from a large phase III Ligelizumab study program including the comparator Omalizumab are awaited and may confirm whether Ligelizumab has the potential to become the first-line treatment option in H1-antihistamine refractory chronic urticaria patients.

This box summarizes key points contained in the article.

Declaration of interest

During the last three years B Wedi has received honorary for educational lectures/advisory boards from ALK-Abelló, Dr. Pfleger, HAL Allergy Novartis, Shire/Takeda, and was recipient of research grant from Shire/Takeda. The author had and has a role as Lead or Principle Investigator in clinical trials of Novartis regarding Omalizumab and Ligelizumab. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the reviewers on this manuscript has acted as a speaker for Novartis and is a sub-investigator in ongoing Phase-3-trial on Ligelizumab. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.