omalizumab

omalizumab, monoclonal antibody used in the treatment of moderate to severe allergic asthma, chronic spontaneous urticaria (hives), and nasal polyps. Omalizumab is the first monoclonal antibody designed to specifically block the effects of the antibody immunoglobulin E (IgE), which plays a key role in allergic reactions. The drug was developed in the 1990s by the pharmaceutical companies Genentech, Tanox, and Novartis and is marketed under the trade name Xolair.

Development and mechanism of action

Research in the 1970s and ’80s highlighted the role of IgE antibodies in allergic reactions, particularly in conditions such as asthma and hives. In response to exposure to certain allergens, IgE binds to immune cells, specifically mast cells and basophils; this binding action triggers the release of histamine and other inflammatory molecules, which then give rise to allergic symptoms. Scientists hypothesized that blocking IgE, and thereby preventing it from binding to its receptors on immune cells and inhibiting the release of inflammatory molecules, would help mitigate allergic reactions.

In the 1990s, recognizing the therapeutic potential of blocking IgE, researchers at Genentech, Novartis, and Tanox collaborated to develop a monoclonal antibody capable of neutralizing circulating IgE, preventing it from binding to immune cells. Through genetic engineering and monoclonal antibody technology, the researchers developed omalizumab, a recombinant humanized antibody designed to specifically target IgE. The drug binds to free IgE molecules, reducing circulating levels of IgE and preventing the antibody from binding to mast cells and basophils. Clinical trials in patients with moderate to severe allergic asthma have shown that omalizumab effectively reduces asthma symptoms, lowers the frequency of allergic reactions, and decreases reliance on corticosteroids.

Approval history

Omalizumab was initially approved by the U.S. Food and Drug Administration (FDA) in 2003 for use in individuals ages 12 and older with severe allergic asthma who do not respond well to inhaled corticosteroids. In 2014 the drug gained additional approval for use against antihistamine-resistant chronic hives, which was followed by approval in 2016 for use in children with allergic asthma and 2020 for difficult-to-treat chronic rhinosinusitis with nasal polyps. These additional approvals have made omalizumab the first monoclonal antibody available for chronic hives and have provided a new option for symptom relief among patients who struggle with nasal congestion, loss of smell, and other consequences of nasal polyps.

Omalizumab was also approved for use in Australia, Canada, and Europe for the treatment of severe persistent allergic asthma in adults and adolescents. The drug ultimately received approval for use in more than 90 countries, with some countries expanding its use to include children ages 6 to 12 with severe asthma and to include hives and nasal polyps treatment. Omalizumab continues to be investigated for additional applications, including its potential use for atopic dermatitis and certain food allergies.

Administration and side effects

Omalizumab is administered by subcutaneous injection about every two to four weeks, with frequency and dose depending on factors such as patient age and weight and IgE serum levels. Its use is associated with various side effects, however, which range from mild to severe. Common mild side effects include headache, fatigue, joint and muscle pain, pain at the injection site, and symptoms of upper respiratory tract infection (e.g., common cold symptoms and sinus infection). Serious side effects include anaphylaxis, potential cardiovascular issues, and serum sickness.