Ligelizumab: Everything You Need to Know

Ligelizumab is a next-generation monoclonal anti-immunoglobulin E (IgE) antibody that shows promise for treating chronic hives that arise spontaneously.

Sporadic hives that occur often, last anywhere from 30 minutes to 24 hours, and flare up unpredictably are called chronic spontaneous urticaria (CSU). Another term for CSU is chronic idiopathic urticaria (CIU). Chronic hives last for more than six weeks.

Ligelizumab is in development at the Swiss multinational drug company, Novartis Pharmaceuticals, as a treatment for CSU. It is still undergoing Phase 3 clinical trials. There isn't a ligelizumab brand name yet; it's currently referred to by the international nonproprietary name QGE031.

This article provides an overview of ligelizumab and explains why this drug is being developed for the treatment of CSU. Read on to learn more about how this IgE-blocking antibody works, what it's designed to treat, potential side effects, and more.

How Ligelizumab Works

Ligelizumab slows the inflammatory process that drives CSU by blocking a specific skin inflammation pathway (IgE/FcεRI) that is associated with chronic hives. Ligelizumab is classified as an "IgE antagonist" for dermatological disorders such as CSU because it neutralizes free serum IgE and inhibits its hive-related inflammatory functions.

As an IgE antagonist, ligelizumab binds to inflammation-inducing IgE in the bloodstream and blocks its ability to trigger an inflammatory process that causes itchy welts (also called wheals) to flare up on the skin. Compared to Xolair (omalizumab)—which is another IgE antagonist for treating CSU—initial studies suggest that ligelizumab (QGE031) provides greater and longer-lasting suppression of IgE.

In most cases, CSU is idiopathic, which means there isn't a clear cause or known medical reason that explains why someone gets this type of hives. Notably, CSU is not caused by an allergic reaction. That said, antihistamines that reduce histamine-driven allergies and inflammation along with drugs that block the inflammatory action of IgE currently treat chronic spontaneous urticaria.

Unfortunately, people with this condition who treat chronic hives with antihistamines often continue to experience itchy and inflamed patches of skin. For patients with moderate-to-severe CSU that isn't controlled with H1-antihistamines alone, or in combination with H2-antihistamines or leukotriene receptor antagonists, ligelizumab shows promise for alleviating chronic spontaneous urticaria by curtailing the inflammatory process that causes itchy wheals (i.e., hives) on the skin.

Studies and Clinical Trials

Currently, Xolair (omalizumab) is the only licensed anti-IgE compound approved by the U.S. Food and Drug Administration (FDA) for clinical use to treat CSU.

Although omalizumab shows therapeutic efficacy for treating severe asthma and CSU, it has limitations, and Novartis wants to develop a better treatment option for chronic hives.

Over the past few years, Novartis has been conducting clinical trials on a next-generation anti-IgE monoclonal antibody (ligelizumab; QGE031), which they hope will overcome some of omalizumab's limitations.

A Phase 2b clinical trial published in The New England Journal of Medicine on Oct. 3, 2019, found that more patients with CSU were completely symptom-free after taking ligelizumab when compared to those taking Xolair.

Another study published in Nature Communications on Jan. 8, 2020, found that ligelizumab can bind to IgE with an 88-fold higher affinity than omalizumab and has the potential to be more effective at treating CSU than omalizumab.

A one-year extension study of Phase 2 clinical trials published on Nov. 13, 2021, in the peer-reviewed journal Allergy confirmed the long-term safety profile of (a 240-milligram dose of) ligelizumab in patients with CSU.

However, in December 2021, Novartis got some bad news when the preliminary results of Phase 3 studies showed that, after a 12-week treatment, ligelizumab succeeded at reducing CSU symptoms but failed to work better than the existing FDA-approved omalizumab treatment.

Other research published in March 2021 related to the treatment of severe asthma suggests that ligelizumab works well but doesn't work better than omalizumab.

In a December 2021 news release, Novartis said that all of their final Phase 3 data regarding ligelizumab as a first-line treatment for CSU will become publicly available when their clinical trials are completed.

Side Effects

Ligelizumab is generally well tolerated by patients with CSU and has relatively few side effects. Because ligelizumab is an injectable, the most common side effect is pain or discomfort at the injection site. During clinical trials, treatment-emergent adverse events (TEAEs) were rare.

Notably, one positive effect of ligelizumab is that by reducing itchiness and the overall disease burden of CSU, sleep quality improves.

Is Ligelizumab Available?

On Jan. 14, 2021, the FDA granted ligelizumab for CSU its Breakthrough Therapy designation for patients who have an inadequate response to H1-antihistamine treatments.

Breakthrough therapies expedite the development and review of new drugs that have the potential to offer a substantial improvement over existing therapies. Breakthrough therapies show potential but aren't a sure thing and don't get FDA approval until Phase 3 trials are complete. Because ligelizumab is still in Phase 3 clinical trials, it isn't available yet.

Is Ligelizumab FDA Approved?

As of early October 2022, ligelizumab hasn't been approved by the FDA. The timeline for ligelizumab FDA approval depends on the results of the Phase 3 trials, which were completed on Aug. 9, 2022.

Summary

Ligelizumab is a next-generation humanized monoclonal antibody that reduces urticaria (hives) by blocking the inflammatory process triggered by immunoglobulin E (IgE).

As of August 2022, the IgE antagonist Phase 3 clinical trial has been completed but isn't approved by the FDA yet. During Phase 2 trials, ligelizumab appeared to treat chronic spontaneous urticaria (i.e., hives without a known cause) better than the existing first-line treatment Xolair (omalizumab).

A Word From Verywell

Living with CSU disrupts quality of life and makes it hard to sleep. One of the most frustrating things about CSU is that it's hard to identify what causes these hives to flare up. The good news is that pharmaceutical advances using humanized monoclonal antibodies show promise for reducing the burden of this skin disorder, improving quality of life, and making it easier to sleep.

Even if ligelizumab (QGE031) doesn't exceed the performance of omalizumab in Phase 3 trials, this existing FDA-approved anti-IgE treatment for CSU works well for many patients.