Novartis reported that the US Food and Drug Administration's (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted unanimously that Xolair (omalizumab) for injection be approved based on a favourable risk benefit profile for the treatment of moderate-to-severe allergic asthma in adults and adolescents. Xolair represents a novel treatment approach and is the first humanized monoclonal antibody developed for the treatment of allergic asthma; it is the only allergic asthma treatment designed to block the IgE antibody, specifically targeting an underlying cause of allergic asthma. Based on the outcome of the Advisory Committee meeting, the sponsors will conduct further discussions with the FDA regarding product labeling and post-marketing commitments.

In clinical trials of moderate to severe patients, Xolair was found to reduce asthma exacerbations (allergic asthma attacks) and enabled many patients to reduce or eliminate usage of inhaled c. Novartis and its partners are seeking approval to market Xolair in the US as a potential maintenance therapy for the prophylaxis of asthma exacerbations and control of asthma symptoms in adults and adolescents (12 years and older) with moderate-to-severe allergic asthma that is inadequately controlled, despite the use of inhaled corticosteroids.

Allergic asthma is the most common form of asthma, a chronic inflammatory disorder of the airways characterized by recurrent episodes of wheezing, breathlessness, chest tightness and coughing that affects approximately 54 million world-wide. In allergic asthma, exposure to an allergen (such as dust, mold or pollen) triggers an allergic cascade, which results in airway obstruction. According to the World Health Organization (WHO) an estimated 180 000 people die from asthma each year worldwide.

"We are very pleased that the advisory committee has recognized the significant benefits that Xolair could offer to people with allergic asthma whose needs are unmet by the existing range of therapies," said Joerg Reinhardt, Head of Development for Novartis Pharma AG. "We look forward to working closely with the FDA to secure approval, so that this unique therapy can be made available to patients at the earliest possible opportunity."

Xolair is being jointly developed under an agreement among Novartis Pharma AG, Genentech, Inc. and Tanox, Inc. The Biologics License Application for Xolair was filed in June 2000 and a supplemental data amendment was submitted in December 2002. The FDA generally follows the advice of its advisory committees, although the agency is not bound by its recommendations. A decision by the FDA is expected in late June 2003.

If approved by the FDA, Xolair would be the first IgE blocker in the US and the first biologic therapy for the treatment of moderate to severe allergic asthma. Furthermore, it is potentially the first asthma product to be administered every two or four weeks. Xolair is designed specifically to block the IgE antibody, a key underlying cause of allergic asthma. When an allergen (e.g. dust, mold, pollen) interacts with (cross-links) IgE bound to mast cells in the human immune system, these cells release inflammatory chemicals such as histamine and leukotrienes that lead to the inflammation and bronchial constriction of allergic asthma. Decreasing the amount of IgE bound to mast cells can disrupt the release of these chemical mediators that cause the clinical symptoms of allergic asthma.

The Advisory Committee's discussions focused on data from two 52-week pivotal Phase III clinical trials with 1 071 allergic asthma patients, as well as data from several supportive safety and efficacy studies. The pivotal trials were designed to investigate a dual benefit of reduction in asthma exacerbations and reduction in inhaled corticosteroid dose. Patients treated with Xolair showed significant improvements in asthma exacerbations and symptoms, and most patients reduced their use of steroids and rescue bronchodilators.

In clinical trials, when used as an add-on therapy to inhaled corticosteroids, Xolair was found to reduce exacerbations (allergic asthma attacks) by approximately 50 per cent. Additionally, the average dose of inhaled corticosteroids in patients taking Xolair in the two pivotal trials was reduced by 83 per cent and 75 per cent respectively, compared with 50 per cent in the placebo groups. Steroid use was discontinued in 40-43 per cent of patients in the Xolair groups compared with 19 per cent in the placebo groups.

The expanded safety database submitted to the FDA includes clinical data from more than 6 000 patients, of which approximately 4 200 patients have been treated with Xolair. In clinical trials, Xolair treatment was generally well tolerated and the frequency of reported adverse events was comparable between the Xolair-treated and control groups. The most frequently observed adverse events included viral infections, sinusitis, upper respiratory infection and headache. Serious adverse events were infrequent and of similar incidence in both the Xolair and control groups. The final labeled efficacy and safety profile description in the product labeling will be determined by the FDA.