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Drugs in Development for Urticaria

Medically Reviewed By Philip Ngo, PharmD

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Urticaria, especially chronic spontaneous urticaria, can be hard to treat. It is also a condition that can have profound effects on patients’ mental well-being and quality of life. Finding more effective treatments for urticaria may improve outcomes for patients managing this condition.


Recent updates to the international urticaria guidelines recommend a three-step treatment approach:

  • First-line treatment: second-generation antihistamines
  • Second-line treatment: omalizumab (Xolair)
  • Third-line treatment: cyclosporine (Gengraf, Neoral, Sandimmune)

Further guidance recommends stepping up or down based on patient response. While this standard approach can be successful, many chronic spontaneous urticaria (CSU) patients remain refractory Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source . However, several treatment options are under investigation that could change this outcome.

This article summarizes some emerging medications that could shape the future of CSU treatment.

New anti-IgE monoclonal antibodies

Omalizumab is the first drug in this category with approval to treat CSU. It has been shown to significantly Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source  reduce itch and wheal scores and improve quality of life. While it has approval for use in adults and children 12 years and older, off-label use in younger children has proved to be effective. Up-dosing is another off-label use of this drug for people who are late responders.

Currently, there are some new players in this category that are making their way through the clinical trials process Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source . Two promising ones are:

  • ligelizumab (QGE031), which has obtained an FDA Breakthrough Therapy designation (an expedited development and review process for drugs that treat serious or life threatening conditions)
  • UB221, which is in earlier phases, was granted approval for phase II trials in 2022

Anti-IL monoclonal antibodies

There are a few monoclonal antibodies (mAbs) targeting various interleukins (ILs) in clinical trials for treating urticaria. One, dupilumab (Dupixent), already has approval for several related conditions, including atopic dermatitis and allergic asthma. This IL-4/13Rα inhibitor is currently in phase III trials.

Other IL inhibitors in earlier phases of investigation include:

Additional monoclonal antibodies

Other mAbs researchers are investigating for use in CSU include:

Bruton tyrosine kinase inhibitors

Bruton tyrosine kinase (BTK) inhibitors are a new generation of biologics that target IgE-mediated responses by inhibiting mast cell activation, basophil signaling, and B-cell function.

Drug candidates in this class include:

A potential advantage of these small molecule biologics is their oral administration.

Other emerging drug candidates

Two other drugs are in development that have unique pathways:

  • AZD1981 Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source is a chemoattractant receptor–homologous molecule expressed on TH2 cell (CRTH2) antagonist. This is a big title for a prostaglandin receptor antagonist. AZD1981 is an oral medication.
  • GSK264264 is a spleen tyrosine kinase inhibitor that is applied topically.

Other potential therapeutic targets

Researchers are also continuing to explore new targets in the pathogenesis of CSU. Areas of exploration include:

  • Mas-related G-protein–coupled receptor X2 (MRGPRX2), which is an important Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source  protein in non-IgE-dependent mast cell degranulation
  • histamine H4 receptors, which are involved in cytokine production and mast cell activation
  • C5a receptors, which are part of the complement system and are linked Trusted Source International Journal of Obesity Peer reviewed journal Go to source  to inflammatory and immune-related conditions


While there is currently one biologic that is standard of care for CSU, several new treatments are on the horizon. As these new drugs make their way to approval, it is important to consider their place in therapy. Some of these potential new treatments may fill a much-needed role in treating CSU in patients who are refractory to standard therapy.

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  1. Dickson MC, et al. (2021). Effects of a topical treatment with spleen tyrosine kinase inhibitor in healthy subjects and patients with cold urticaria or chronic spontaneous urticaria: Results of a phase 1a/b randomised double-blind placebo-controlled study.
  2. Feng Y, et al. (2023). Mechanism of activation and biased signaling in complement receptor C5aR1.
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  7. Sanofi and Regeneron. (2023). Media update: Sanofi and Regeneron provide update on Dupixent® (dupilumab) sBLA for chronic spontaneous urticaria [Press release].
  8. Mehta P, et al. (2020). Enigmatic histamine receptor H4 for potential treatment of multiple inflammatory, autoimmune, and related diseases.
  9. Metz M, et al. (2021). Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial.
  10. Novartis Pharma AG. (2023). Novartis data show potential of remibrutinib as an oral treatment for chronic spontaneous urticaria providing significant symptom improvement as early as Week 2 [Press release].
  11. Novartis Pharma AG. (2021). Novartis ligelizumab (QGE031) receives FDA Breakthrough Therapy designation for patients with chronic spontaneous urticaria (CSU) [Press release].
  12. Oliver ET, et al. (2019). Effects of an oral CRTH2 antagonist (AZD1981) on eosinophil activity and symptoms in chronic spontaneous urticaria.
  13. Yosipovitch G, et al. (2023). Current and emerging therapies for chronic spontaneous urticaria: A narrative review.
  14. Zuberbier T, et al. (2022). Chronic spontaneous urticaria guidelines: What is new?

Medical Reviewer: Philip Ngo, PharmD
Last Review Date: 2024 Mar 12
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