Emerging treatments for chronic urticaria

ABSTRACT

Introduction

Across the globe, chronic urticaria (CU), i.e. chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CINDU), is common, long-persisting and difficult to manage. Still, at least one-fifth is not sufficiently controlled by guideline-recommended treatment with H1-antihistamines and add-on therapy with the anti-IgE monoclonal antibody omalizumab.

Areas covered

Using PubMed, ClinicalTrials.gov, Congress websites, and websites of the manufacturers, this review explored the pipeline, namely anti-IgE-, anti-cytokine-, anti-receptor biologics, and small molecules, in clinical development for CU.

Expert opinion

The CU pipeline is promising. While three omalizumab biosimilars are investigated, the assumed early approval of ligelizumab will expand the effective and safe anti-IgE approach observed with omalizumab. For other anti-IgEs like UB-221, the development is behind. Data are too limited so far to clearly define the role of anti-cytokine and anti-cytokine receptor biologics such as dupilumab, tezepelumab, mepolizumab, benralizumab, and CDX-0159, of which only dupilumab is actually investigated in phase 3. Among three selective oral BTK inhibitors, remibrutinib, rilzabrutinib, and fenebrutinib, the development of remibrutinib is most advanced (phase 3). As the pipeline addresses different targets, study results will give deeper insights into the pathomechanisms of CU. Hopefully, in the next future additional approved and also more targeted approaches will be available.

KEYWORDS:

• Chronic urticaria
• treatment
• pipeline
• anti-IgE
• dupilumab
• BTK inhibitors

Article highlights

• Until 2014, only H1-antihistamines were approved for the treatment of chronic urticaria (CU); however, they do not sufficiently control symptoms in most patients

• Approval of the anti-IgE mAb omalizumab in 2014 for chronic urticaria was a milestone. Up to 80% of patients are well controlled with this agent.

• The clinical development pipeline includes next-generation anti-IgE mAbs, anti-cytokine-, anti-receptor biologics and small molecules.

• Anti-IgE mAb Ligelizumab has demonstrated efficacy and safety and superiority to omalizumab in phase 2 and in a 52-week extension study.

• Anti-IgE ligelizumab might close the gap for the estimated one-fifth of patients who are not controlled by using omalizumab.

• Selective Bruton’s tyrosine kinase inhibitors remibrutinib, rilzabrutinib, and fenebrutinib have been investigated in chronic spontaneous urticaria (CSU). The development of remibrutinib is most advanced, in phase 3.

• Dupilumab, tezepelumab, mepolizumab, benralizumab, or CDX-0159 might emerge as better choice in yet to be defined urticaria endotypes in which targeting other structures aside from IgE might be more useful.

• Pipeline drugs are investigated not only in chronic spontaneous urticaria (CSU) but also in chronic inducible urticaria (CINDU).

This box summarizes key points contained in the article.

Declaration of interest

The author received personal fees for educational lectures and advisory boards from Novartis, Shire/Takeda, ALK-Abéllo, HAL Allergy, Bencard, CSL-Behring, Leo Pharma, and ThermoFisher Scientific; a research grant from Shire/Takeda, outside the submitted work. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is a Medical Advisor for Uriach Pharma, Genentech, Novartis, FAES, GSK, Sanofi–Regeneron, Amgen, Thermo Fisher Scientific, Almirall, Leo Pharma, and Celldex. They have also received research grants from Uriach Pharma, Novartis, Grants from Instituto Carlos III-FEDER and have participated in educational programs for Uriach Pharma, Novartis, Genentech, Menarini, LEO PHARMA, GSK, MSD, Almirall, Sanofi-Regeneron, and Avene. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.