Omalizumab Injection (Xolair)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved Genentech’s omalizumab, the first biotechnology drug for the treatment of asthma. Omalizumab is a monoclonal antibody that binds to human immunoglobulin E (IgE), a major mediator of allergy-related asthma. The drug is given by subcutaneous injection every 2 or 4 weeks. It is manufactured by Genentech Inc and is jointly marketed by Genentech and Novartis Pharmaceuticals as Xolair.
Indications
Omalizumab is indicated in adults or adolescents (12 years of age and older) with moderate-to-severe persistent asthma with positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled steroids.1
Dosage
The recommended dose is 150-375 mg administered subcutaneously every 2 or 4 weeks. Serum total IgE levels before the start of treatment and body weight determine the dose and frequency. Doses greater than 150 mg should be divided among more than one injection site and not more than 150 mg per site.1
Xolair is available as a single-use vial designed to deliver 150 mg.
Potential Advantages
Omalizumab has been reported in studies to reduce the number of exacerbations, asthma-related emergency room visits, and hospitalizations and to improve asthma symptoms and pulmonary function compared to placebo.1-3
Potential Disadvantages
A higher incidence of malignant neoplasms was reported with omalizumab in clinical studies, 20 of 4127 (0.5%) compared to 5 of 2235 (0.2%) for placebo. Rare incidence of anaphylaxis has also been reported. Total serum IgE levels are elevated during omalizumab therapy and for up to 1 year after discontinuation of therapy. The long-term implications of exposure to omalizumab or elevated total IgE levels after discontinuation of omalizumab is not known. The most common side effect is injection site reactions (eg, bruising, redness, burning, stinging, pain, induration, mass, inflammation) that occurred in 45% of patients and was severe in 12%.1
Comments
IgE plays an important role in allergic immune response including bronchial asthma. Omalizumab is a recombinant humanized monoclonal antibody that selectively binds to free human IgE. This reduces binding to various cells such as masts cells, monocytes, eosinophils, and dendrite cells blunting the release of mediators/cytokines.5 Phase III clinical trials (pooled of 3 studies) in children (n = 334; ages 6-12) and adults (n = 1071) suggest that omalizumab administration reduced unscheduled asthma-related outpatient visits, emergency room visits, and hospitalizations. The rate ratios and 95% CI were 0.60 (0.44-0.81); P < 0.01; 0.47 (0.24-1.01); P = 0.05, and 0.08 (0.00-0.25); P < 0.01, respectively.2 Omalizumab has also been shown to reduce exacerbations compared to placebo and permitted reduction of the steroid dose.6 In patients requiring moderate-to-high doses of inhaled corticosteroids, the addition of omalizumab has resulted in an improvement in asthma-related quality of life (QoL) both in a steroid stable and steroid reduction phases.3,4 The domains of the survey include activities, emotion, symptoms, and environmental exposure. The overall mean change in QoL was 0.90 units in a 32-question 7-point scale vs 0.62 in the steroid-phase (P < 0.001) and 0.99 vs 0.66 in the steroid-reduction phase (P < 0.001).7 A change of 0.5 or greater is considered as clinically meaningful. Omalizumab does not appear to reduce exacerbations in patients who had FEV1 > 80% and those who require maintenance with oral steroids.1 The wholesale cost of omalizumab is $433 per 150-mg vial. Four-week cost ranges from $433 to $2590 depending on pretreatment level of serum IgE and body weight.
Clinical Implications
Omalizumab offers a second-line novel approach to managing asthma patient. Adults and adolescents with moderate-to-severe asthma inadequately controlled on inhaled steroids, with frequent exacerbations, FEV1 < 80%, not on oral steroid maintenance, and positive skin test to a perennial aeroallergen may be candidates for this expensive biotech drug.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.
References
1. Xolair Product Information. Genentech, Inc. June 2003.
2. Corren J, et al. J Allergy Clin Immunol. 2003;111:87-90.
3. Busse W, et al. J Allergy Clin Immunol. 2001;108:184-190.
4. Finn A, et al. J Allergy Clin Immunol. 2003;111:278-284.
5. Milgrom H. Arch Dis Child. 2003;88:71-74.
6. Buhl R et al. Eur Respir J. 2002;20(5):1088-1094.
7. Busse W, et al. J Allergy Clin Immunol. 2002;109(1 suppl):S291.
The FDA has approved Genentechs omalizumab, the first biotechnology drug for the treatment of asthma.
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