P&T Portfolio: Xolair

August 18, 2003

Xolair - Omalizumab should be used as a second-line treatment option for patients with moderate to severe persistent asthma

 

HEALTH-SYSTEM EDITION

P & T PORTFOLIO

Generic name

Omalizumab subcutaneous

Proprietary name/manufacturer

Xolair/Genentech, Novartis

FDA-approved indication

Treatment of adults and adolescents (12 years of age and older) with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids

Pharmacology

Omalizumab is a recombinant humanized (chimeric) monoclonal antibody directed against immunoglobulin E (IgE). It inhibits the binding of IgE to the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells and basophils. The reduction in surface-bound IgE on Fc epsilon RI-bearing cells limits the degree of release of mediators of the allergic response. Treatment with omalizumab also reduces the number of Fc epsilon RI receptors on basophils in atopic patients.

Efficacy

The approval of omalizumab was based on efficacy data from three multicenter placebo-controlled clinical trials involving 1,412 symptomatic patients with moderate to severe persistent asthma who had a positive skin test reaction to a perennial aeroallergen. All patients were also being treated with inhaled corticosteroids and short- acting beta agonists; in addition, the third study allowed long-acting beta agonists and oral corticosteroid.

Efficacy in these trials was based on the number of asthma exacerbations per patient, defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of the baseline dose of inhaled corticosteroid. Study results showed that exacerbations per patient were reduced in patients receiving omalizumab compared with placebo in studies 1 and 2, but not in study 3. In all three studies, a reduction of asthma exacerbations was not observed in omalizumab-treated patients who had baseline FEV1>80% or in patients who required oral steroids as maintenance therapy. Comparative clinical studies between omalizumab and other agents used to treat asthma are not available. Omalizumab has not been shown to alleviate asthma exacerbations acutely, and it is not indicated for the treatment of bronchospasm or status asthmaticus.

Adverse effects

The most common adverse effects, seen in 2% to 12% of patients, included: severe injection-site reactions, arthralgia, pain, leg pain, dizziness, fatigue, fracture, arm pain, pruritus, dermatitis, and earache.

Pharmacokinetics

Absolute bioavailability (SC)62%
Volume of distribution (SC)78 ml/kg
MetabolismClearance of omalizumab involves IgG clearance processes as well as clearance via specific binding and complex formation with IgE. IgG is degraded in the liver reticuloendothelial system and endothelial cells.
ExcretionBile (intact IgG)
Half-life26 days

 

Warnings

• Malignant neoplasms were observed in 0.5% of omalizumab-treated patients compared with 0.2% of control patients in clinical studies.

• Anaphylaxis has occurred within two hours of the first or subsequent administration of omalizumab.

Precautions

• Omalizumab should not be used for acute bronchospasm or status asthmaticus.

• Corticosteroid reduction should be done gradually.

Conclusion/comments

Omalizumab is an anti-IgE monoclonal antibody that has demonstrated efficacy in the treatment of patients with moderate to severe persistent allergic asthma when administered subcutaneously at two- or four-week intervals. It is the first of a new class of therapies that target IgE, which triggers the release of inflammatory mediators and plays a major role in allergic asthma symptoms. Patients with mild and moderate asthma are usually well controlled by the use of inhaled cortico-steroids and beta agonists, but some patients are more difficult to manage because they remain symptomatic and suffer from frequent exacerbations.

Omalizumab was approved as second-line treatment in patients who have failed after first-line treatments. Due to its high cost and need for subcutaneous administration, guidelines for the use of omalizumab should be developed, along with a patient education program.

 

Published August 2003. Content based on medical literature and product information available at that time.

 

 

P&T Portfolio: Xolair. Drug Topics Aug. 18, 2003;147:HSE11.