Xolair's proposed EU label may prove disappointing for Novartis

Asthma is a common chronic disorder of the airways, characterized by airway inflammation, airway hyperresponsiveness, and airway narrowing that is reversible, with treatment or spontaneously.

There are estimated to be around 10 million diagnosed asthma patients in the UK, France, Germany, Italy and Spain, of which around 1.8 million (18%) have severe persistent asthma. While representing a small percentage of asthma patients, these patients account for much of the morbidity, mortality, and cost of the disease.

Proposed label does not include exacerbations reduction

In June 2004, Novartis submitted an application for the European approval of Xolair (omalizumab), a novel anti-IgE therapy. This application seeks a proposed label that indicates Xolair as add-on therapy for the prevention of asthma exacerbations and control of asthma symptoms for adolescent and adult patients with severe persistent allergic asthma who remain inadequately controlled despite treatment with high-dose inhaled corticosteroids plus a long-acting beta-2 agonist.

One of the studies the application is based on is the INNOVATE study, which used reductions in severe exacerbation (acute worsening of symptoms) as the primary endpoint. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion following its meeting on July 26-28, 2005, paving the way for approval later this year.

However, the proposed label only indicates that Xolair be used for control of asthma symptoms and does not include an indication for the prevention of asthma exacerbations. It is possible that the EU label may include similar wording to that used on the label, which simply states that "Xolair has been shown to decrease the incidence of asthma exacerbations".

Different US and EU labels

The proposed EU label differs from the label in key aspects that will limit the potential number of patients who will be prescribed Xolair. Firstly, in the , Xolair may be prescribed for patients with moderate to severe persistent asthma, while the EU label is limited to patients with severe persistent asthma.

Secondly, the label states that Xolair may be prescribed to patients whose symptoms are inadequately controlled on inhaled corticosteroids alone, compared to the EU label, which limits use to those inadequately controlled despite using inhaled corticosteroids plus a long-acting beta-2 agonist.

An effective therapy for some

There is no doubt that, in some patients, Xolair is dramatically effective, resulting in the withdrawal of oral corticosteroids, which are associated with adverse effects when used for long periods of time. However, the drug is only indicated for use in patients with atopic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen. As only around 40% of adult asthma cases can be attributed to sensitization to common inhaled allergens, there remains a need for an effective therapy for non-atopic moderate-severe asthmatics.

Xolair's high costs, at approximately $12,000 per annum, its restrictive label, and the lack of an indication for the prevention of asthma exacerbations will lead to modest uptake rates in the EU. As a result of this, it would make sense for Novartis and Genentech to focus their energies on the market, as seems likely at present.

Indeed, despite the drug's high costs, US sales hit around the $200 million mark in 2004, which according to Datamonitor research, is forecast to rise to $650 million by 2010. The land of the Big Apple is likely to remain the apple in Novartis and Genentech's eyes as far as Xolair is concerned.

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