Omalizumab, sold under the brand name Xolair among others, is an injectable medication to treat severe persistent allergic forms of asthma, nasal polyps, urticaria (hives), and immunoglobulin E-mediated food allergy. Omalizumab is a recombinant DNA-derived humanized IgG1 monoclonal antibody which specifically binds to free human immunoglobulin E (IgE) in the blood and interstitial fluid and to the membrane-bound form of IgE (mIgE) on the surface of mIgE-expressing B lymphocytes. In 1987, Tanox filed its first patent application on the anti-IgE drug candidate. Omalizumab was approved for medical use in the United States in June 2003, and authorized in the European Union in October 2005.
Medical uses In the United States, omalizumab is indicated to treat moderate to severe persistent asthma; chronic rhinosinusitis with nasal polyps; immunoglobulin E (IgE)-mediated food allergy; and chronic spontaneous urticaria. In the European Union, omalizumab is indicated to treat allergic asthma, chronic (long-term) spontaneous urticaria (itchy rash), and severe chronic rhinosinusitis with nasal polyps. In Australia, omalizumab is indicated to treat allergic asthma and chronic spontaneous urticaria.
Allergic asthma Omalizumab is used to treat people with severe, persistent allergic asthma that is not controlled with oral or injectable corticosteroids. Those patients have already failed step I to step IV treatments and are in step V of treatment. Such a treatment scheme is consistent with the widely adopted guidelines for the management and prevention of asthma, issued by Global Initiative of Asthma (GINA), which was a medical guidelines organization launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health (US), and the World Health Organization. A 2014 Cochrane review found that omalizumab was effective in reducing exacerbations and hospitalisations related to asthma when used as an adjunct to steroids.
Chronic spontaneous urticaria Omalizumab is indicated for chronic spontaneous urticaria in adults and adolescents (>12 years old) poorly responsive to H1-antihistamine therapy. When administered subcutaneously once every four weeks, omalizumab has been shown to significantly decrease itch severity and hive count.
Food allergy In February 2024, the US Food and Drug Administration (FDA) approved an update to the prescription label to include an indication for immunoglobulin E-mediated food allergy for the reduction of allergic reactions, including anaphylaxis, which may occur with accidental exposure to one or more foods. Omalizumab can be used as a monotherapy or in combination with oral immunotherapy.
Chemistry and formulations Omalizumab is a glycosylated IgG1 monoclonal antibody produced by cells of an adapted Chinese hamster ovary (CHO) cell line.
Mechanism of action The rationale for designing the anti-IgE therapeutic antibodies and the pharmacological mechanisms of anti-IgE therapy have been summarized in articles by the inventor of the anti-IgE therapy. Unlike an ordinary anti-IgE antibody, it does not bind to IgE that is already bound by the high affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and antigen-presenting dendritic cells. Perhaps the most dramatic effect, which was not foreseen at the time when the anti-IgE therapy was designed and which was discovered during clinical trials, is that as the free IgE in patients is depleted by omalizumab, the FcεRI receptors on basophils, mast cells, and dendritic cells are gradually down-regulated with somewhat different kinetics, rendering those cells much less sensitive to stimulation by allergens. Thus, therapeutic anti-IgE antibodies such as omalizumab represent a new class of potent mast cell stabilizers. This is now thought to be the fundamental mechanism for omalizumab's effects on allergic and non-allergic diseases involving mast cell degranulation. Many investigators have identified or elucidated a host of pharmacological effects, which help bring down the inflammatory status in omalizumab-treated patients.
IgE in allergic diseases In conjunction with achieving the practical goal to investigate the applicability of the anti-IgE therapy as a potential treatment for allergic diseases, the many corporate-sponsored clinical trials of TNX-901 and omalizumab on asthma, allergic rhinitis, peanut allergy, chronic idiopathic urticaria, atopic dermatitis, and other allergic diseases, have helped define the role of IgE in the pathogenesis of these prevalent allergic diseases. For example, the clinical trial results of omalizumab on asthma have unambiguously settled the long debate on whether IgE plays a central role in the pathogenesis of asthma. Numerous investigator-initiated case studies or small-scale pilot studies of omalizumab have been performed on various allergic diseases and several non-allergic diseases, especially inflammatory skin diseases. These diseases include atopic dermatitis, various subtypes of physical urticaria (solar, cold-induced, local heat-induced, or delayed pressure-induced), and a spectrum of relatively less prevalent allergic or non-allergic diseases or conditions, such as allergic bronchopulmonary aspergillosis, cutaneous or systemic mastocytosis, bee venom sensitivity (anaphylaxis), idiopathic anaphylaxis, eosinophil-associated gastrointestinal disorder, bullous pemphigoid, interstitial cystitis, nasal polyps, and idiopathic angioedema.
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