Xolair® significantly reduces asthma attacks and emergency treatment in patients most at risk of asthma-related death

 

Basel, February 15, 2005 - A new analysis of results from seven clinical studies published today1 shows that Xolair® (omalizumab) - a first-in-class therapy that targets a root cause of allergic disease - significantly reduced the number of asthma exacerbations ('attacks') and almost halved the rate of emergency visits.  The studies involved more than 4,300 patients with severe persistent asthma, who were inadequately controlled despite receiving the therapy specified in current guidelines.

 

The summary of data appears in Allergy, the peer-reviewed journal of the European Academy of Allergology and Clinical Immunology (EAACI).  The same publication contains the first detailed results2 from one of the trials, INNOVATE, indicating that "omalizumab is an effective add-on therapy for these difficult-to-treat patients who have an important unmet medical need."  Results from all seven studies are included in the application submitted to the Committee for Medicinal Products for Human Use (CHMP), which is currently evaluating whether Xolair should be approved for use in EU countries.

 

Xolair is a monoclonal antibody that is given by subcutaneous injection every two or four weeks, and targets IgE (immunoglobulin E) which triggers the cascade of inflammatory symptoms in patients affected by diseases such as allergic asthma.  Its efficacy is demonstrated by the review published in Allergy, in which data from seven studies were pooled to determine the effect of Xolair on asthma exacerbations in patients with severe persistent asthma.  Xolair was added to current asthma therapy and compared either with placebo (in five double-blind studies), or with current asthma therapy alone (in two open-label studies).

 

More than 90% of patients across the seven studies met the criteria for severe persistent asthma laid down in the Global Initiative for Asthma (GINA) 2002 guidelines.  The review demonstrates that Xolair reduced the rate of asthma exacerbations by 38% vs. control (p < 0.0001).  Overall, the total number of emergency visits was reduced by 47% in Xolair-treated patients (p < 0.0001), including reductions of 61% in emergency room visits (p = 0.013) and 52% in hospital admissions (p = 0.041).

 

Xolair was also shown to reduce the need for inhaled corticosteroids, to improve asthma symptoms and lung function, and to improve asthma-related quality of life.  The authors of the report, led by the editor of Allergy, Prof Jean Bousquet of Hôpital Arnaud de Villeneuve, Montpellier, France, stated: "The decreases in the rates of asthma exacerbations and those requiring emergency care, are highly relevant to the management of patients with severe asthma.

 

"Severe exacerbations are responsible for the mortality associated with asthma, and contribute heavily to the morbidity and costs of the disease.  Indeed, the 5-10% of asthma patients with the most severe form of the disease contribute some 50% of the total costs associated with asthma.3  Decreasing the rate of exacerbations in patients with severe asthma is likely to be associated with improvements in quality of life and decrease burdens on patients and health care systems, as well as potentially saving lives."

 

A total of 15 million people worldwide are estimated to suffer from severe persistent asthma4 and are therefore at high risk of experiencing severe and potentially fatal attacks.5,6  One in every 250 deaths throughout the world is thought to be due to asthma-related causes,4 and the total costs associated with asthma are greater than those for tuberculosis and HIV/AIDS combined.7  With the number of asthma cases predicted to rise by another 100 million by 2025, the human and social burden could increase even further.4

 

Importantly, the data show that response to Xolair was even more pronounced in individuals known to be at greatest risk of asthma-related death.  A sub-analysis of three placebo controlled studies8 showed that Xolair reduced the rate of asthma exacerbations by 55% vs. placebo (p < 0.0004) in 254 patients who were defined as high-risk on the basis of an overnight hospitalisation, intensive care unit stay or emergency room visit in the past year, or any prior intubation.

 

The review published today incorporates results from INNOVATE, a randomised, double-blind, placebo-controlled study in 419 patients aged 12-75 who were inadequately controlled despite treatment with high-dose inhaled corticosteroids and long acting beta2 agonists (i.e. step 4 therapy in the GINA guidelines).  Patients were recruited for the 28-week study at 108 centres in Australia, Belgium, Canada, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand, South Africa, Spain, UK, and US.  The rate of clinically significant asthma exacerbations (i.e. those requiring rescue systemic corticosteroid therapy) was significantly reduced by 26% (p = 0.043), when adjusted for an observed imbalance in asthma exacerbation history prior to randomisation into the trial.  Without taking this baseline imbalance into account, a similar magnitude of effect was seen (i.e. a 19% reduction) but this did not reach statistical significance.  Unadjusted data were used in the pooled analysis.

 

In the same difficult-to-treat group of patients, Xolair halved the number of severe asthma exacerbations, i.e. those requiring rescue systemic corticosteroid therapy in which lung function was also below 60% of the patient's personal best (49 events with Xolair vs. 100 with placebo, p = 0.002).  In addition, Xolair significantly reduced the total number of emergency visits for asthma (p = 0.038).

 

The authors of the study, led by Prof Marc Humbert of Hôpital Antoine Beclere, Clamart, France, concluded: "Patients' quality of life was improved, as were symptoms and lung function, and both patients and investigators considered omalizumab an effective treatment.  Omalizumab was well-tolerated, with no evidence of clinically significant concerns of treatment.  These clinically meaningful benefits demonstrate the usefulness of omalizumab as an add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet medical need despite best available therapy."

 

An estimated 33,000 patients have been referred for Xolair treatment in the US since it was launched there in July 2003, and Xolair is also approved in Australia, Brazil, Canada, New Zealand and Venezuela.  It has been developed under an agreement between Novartis Pharma AG, Genentech, Inc., and Tanox, Inc.  Health authorities in the EU are expected to announce their decision on Xolair approval later this year.

 

The foregoing release contains certain forward-looking statements that can be identified by terminology such as "predicted to rise," "could increase," "are expected to," or similar expressions, or by discussions regarding the potential that Xolair will be approved for marketing, or regarding any potential revenues from Xolair.  Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Xolair to be materially different from any future results, performance or achievements expressed or implied by such statements.  There can be no guarantee that Xolair will be approved for sale in any market.  In particular, management's expectations regarding commercialization of Xolair could be affected by, among other things, uncertainties relating to clinical trials; new clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; as well as other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission.  Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected.  Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

 

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health.  In 2004, the Group's businesses achieved sales of USD 28.2 billion and a net income of USD 5.8 billion.  The Group invested approximately USD 4.2 billion in R&D.  Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world.  For further information please consult http://www.novartis.com.

 

1 Bousquet J et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy Mar 2005

2 Humbert M et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy Mar 2005

3 Barnes PJ, Jonsson B, Klim JB. The costs of asthma. Eur Respir J 1996;9:636-642

4 GINA. The Global Burden of Asthma Report 2004

5 Tough SC, Hessel PA, Ruff M, Green FH, Mitchell I, Butt JC. Features that distinguish those who die from asthma from community controls with asthma. J Asthma 1998;35:657-665

6 Turner MO, Noertjojo K, Vedal S, Bai T, Crump S, Fitzgerald JM. Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med 1998;157:1804-1809

7 European Respiratory Society. The European Lung White Book: The First Comprehensive Survey on Respiratory Health in Europe. 2003

8 Holgate S, Bousquet J, Wenzel S, Fox H, Liu J, Castellsague J. Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality. Curr Med Res Opin 2001;17:233-240

 

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John Gilardi    
                                  
Novartis Global Media Relations  
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john.gilardi@group.novartis.com  
                                  
John Taylor                        
                                   
Novartis Pharma Communications     
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john.taylor@pharma.novartis.com