Ligelizumab (QGE031) is currently being developed by Novartis for the treatment of allergic diseases mainly asthma and chronic spontaneous urticaria. Allergic diseases are dependent on the development of increased IgE levels. Allergen-specific IgE plays a role in the inflammatory cascade of allergic responses. Allergic individuals with elevated IgE levels have increased allergic mediators (e.g. histamine, leukotrienes) after exposure to allergens.
Omalizumab (Xolair) was the first anti-IgE therapy and humanized monoclonal antibody for the treatment of moderate to severe persistent allergic asthma. Omalizumab bind to the IgE molecule and prevents it from binding IgE receptors. This dampens the allergic response in susceptible individuals. It is also now approved for chronic idiopathic (spontaneous) urticaria.
Ligelizumab (QGE031) is a fully humanized IgG1 monoclonal antibody directed against human IgE that binds with greater affinity than omalizumab (Xolair). Ligelizumab (QGE031) is designed to obtain greater suppression of IgE bound to mast cells and basophils compared to Xolair, this might translate into superior interruption of the allergic cascade and greater clinical efficacy in asthmatic patients.
A recent study published in The Journal of Allergy and Clinical Immunology tested 3 dose levels (24, 72 and 240 mg administered every 2 weeks) of Ligelizumab (QGE031) in patients with asthma and compared their effect on allergic airway and skin responses with those of Xolair (omalizumab) and placebo.
Ligelizumab (QGE031) enhanced and prolonged the suppression of IgE receptors on basophils, led to a more pronounced inhibition of allergy skin test responses and decreased the response of asthma allergy challenges more effectively than Xolair (omalizumab). Whether the enhanced pharmacodynamic response of Ligelizumab (QGE031) translates into clinical benefits in patients with severe asthma and chronic urticaria is unknown, but it needs to be evaluated in patient populations in the future.
Ligelizumab (QGE031) was well tolerated in adults, the most common adverse events were nasopharyngitis and worsening asthma. All adverse events were mild to moderate in nature. No cases of anaphylaxis or hives were reported.
Ligelizumab (QGE031) is an exciting new medication being studied for allergic diseases. In studies it has shown grater inhibition than Xolair (omalizumab) in binding to IgE. Besides asthma this could have a great impact for patients who have chronic idiopathic urticaria. As we have described in older posts, patients who have chronic hives may sometimes go up 12 weeks between injections for Xolair (omalizumab). If Ligelizumab (QGE031) binds to IgE with greater affinity (up to 3-fold greater), theoretically for patients with chronic urticaria they may be able to go a longer period of time between injections.
The patent for Xolair (omalizumab) is set to expire in the European Union, August 2017 and in the United States, January 2020.
Stay tuned for more info on Ligelizumab (QGE031) as it goes through clinical drug trials.
Update: January 20, 2020
Ligelizumab (QGE031) in a phase 2b trial demonstrated rapid onset of action, dose-dependent efficacy and superiority to omalizumab. More than 50% of patients taking 240 mg of ligelizumab were complete responders, a response rate twice that seen in omalizumab. Average relapse time for omalizumab was 4 weeks compared to 10 weeks for ligelizumab. Phase 3 studies have been initiated and more than 2000 patients will be recruited.
Another anti-IgE drug, UB-221 is being evaluated in phase 1 trials. UB-221 has an 8 fold higher binding affinity to free IgE and down-regulates IgE synthesis by binding to IgE on CD23.