Basel, September 19, 2005 - New long-term data show that Xolair® (omalizumab), a first-in-class monoclonal antibody for treating severe allergic asthma, helped patients to maintain control of their disease and was safe and well-tolerated in studies lasting more than three years. The data were presented today at the European Respiratory Society (ERS) congress in Denmark, along with results from seven clinical studies showing that Xolair significantly improved the lung function of patients.
Long-term control of severe allergic asthma was demonstrated in a study spanning 180 weeks of observation. The design included a 32-week randomised, double-blind, parallel-group, placebo-controlled study, followed by a 96-week open-label extension and a further 52-week extension.
As a result, patients completing the study and both extensions had been treated for more than three years. Disease control was maintained throughout the follow-up period in Xolair patients, who exhibited lower than expected changes in lung function and reduced use of inhaled corticosteroids (ICS).[1]
"These results confirm that omalizumab potentially provides an important breakthrough in the fight against allergic asthma," said Prof. Marc Humbert of the Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Clamart, France. "Many people suffering from severe asthma have a substantially impaired quality of life and endure the constant fear that their next attack may prove fatal. By reducing exacerbations and the burden of disease, anti-IgE therapy offers a new approach to the treatment of this intractable condition."
Xolair manages asthma by targeting an underlying cause of allergic disease (up to 90% of asthma being allergic in origin[2]). It is designed to block the action of IgE, which is responsible for initiating the cascade of inflammatory symptoms such as airway constriction, mucus production, wheezing and shortness of breath. Xolair has been shown to decrease asthma exacerbations in some of the most difficult-to-treat patients whose condition remains inadequately-controlled despite the best conventional therapy, including inhaled corticosteroids, long-acting beta2-agonists and other controller medications.
The Committee for Medicinal Products for Human Use (CHMP) recently gave a positive opinion on initial marketing authorisation for Xolair, opening the way for approval by the European Commission and for the therapy to become available in EU countries.
More about the three-year study demonstrating efficacy and safety
In the 32-week placebo controlled study, 341 patients received Xolair (at least 0.016 mg/kg/IgE [IU/mL] every four weeks) or placebo. A total of 222 patients entered Extension 1 (96 weeks), 178 of whom continued into Extension 2 (52 weeks). Patients in the extensions maintained stable lung function (measured by forced expiratory volume in one second, or FEV1). Mean FEV1 was 2.24 litres at the start of Extension 1 and 2.26 litres at the end of Extension 2, indicating persistency of therapeutic benefit from Xolair. In addition, more than 80% of patients had good/excellent asthma control during the extensions. Patients receiving inhaled corticosteroids at the start of Extension 1 and remaining on the same steroid reduced their ICS use by an average of 11% between the start of Extension 1 and the end of Extension 2.
In this long-term study, the overall incidence of adverse events was similar in the Xolair and placebo groups during the 32-week placebo-controlled study and Extension 1 (i.e. approximately 80% in both groups). During Extension 2, 134 patients (75%) had at least one adverse event, most of which were mild to moderate in severity. Serious adverse events remained infrequent during the second extension (4.5%) and were deemed by the treating physician to be unrelated to Xolair.[3]
Improvements in lung function and quality of life
Pooled data were also presented from seven trials in which allergic asthma patients (93% of whom had severe persistent disease) received Xolair as an add-on to inhaled corticosteroids, with or without oral corticosteroids and long-acting beta2-agonists. Out of 4,308 patients in the studies, FEV1 data were available for 3,537 patients (Xolair 2,443; control 1,094). Among Xolair recipients, 29.1% increased their FEV1 by >=200mL while 17.5% showed a >=200mL decrease. In the control group, 26.4% had a >=200mL increase in FEV1 and 26.1% had a >=200mL decrease. This equates to a net benefit of 11.6% for Xolair patients versus 0.3% for control (P<0.0001).[4]
Results from the same seven studies showed that add-on Xolair significantly improved patients' asthma-related quality of life, measured using the Juniper Adult Asthma Quality of Life Questionnaire (AQLQ). Quality of life data were available for 2,288 patients (Xolair 1,258; control 1,030). Those receiving Xolair had a mean increase of 1.01 points in their overall AQLQ score, compared to 0.67 in the control group (P<0.0001). Significantly more patients achieved a clinically meaningful improvement (i.e. an improved score of at least 0.5) in their AQLQ score from baseline in the Xolair group (66.3%) than the control group (53.2%, p<0.0001).[5]
Anti-IgE and severe asthma
Xolair has been available in the US for treating moderate to severe allergic asthma since July 2003, and as of 30 June 2005 it had been prescribed to more than 45,000 patients. In July 2005 the CHMP gave a positive opinion on Xolair in the EU, and approval is expected later this year. If approved by the European Commission, Xolair will be indicated as add-on therapy to improve asthma control in adult and adolescent patients (12 years of age and above) with severe persistent allergic asthma, who had the following, despite daily high-dose inhaled corticosteroids plus a long-acting inhaled beta2-agonist:
Xolair is also approved in Australia, Brazil, Canada, Dominican Republic, Guatemala, Israel, New Zealand and Venezuela. It was developed under an agreement between Novartis Pharma AG, Genentech, Inc., and Tanox, Inc.
Around 300 million people worldwide have asthma,[6] and an estimated 15 million of them suffer from a severe form of the disease.[7] Their health and quality of daily life are often severely affected, and more than 180,000 people are believed to die from asthma each year throughout the world.[8]
The potential benefits of anti-IgE therapy are already recognised in treatment guidelines such as those developed by the Global Initiative for Asthma (GINA). These recommend anti-IgE therapy as add-on treatment for patients with severe allergic asthma that is inadequately controlled by standard clinical options.[9]
The foregoing release contains certain forward-looking statements that can be identified by terminology such as "potentially", "opening the way," "is expected," "will be", or similar expressions, or by express or implied discussions regarding the potential that Xolair will be approved for sale in any additional markets, or regarding any potential future 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 additional market, or that it will achieve any particular sales level. In particular, management's expectations regarding commercialization of Xolair could be affected by, among other things, uncertainties relating to clinical trials; new clinical data, or additional analysis of existing 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.
About Novartis
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Novartis Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 83,700 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
References
[1] Chung KF et al. Long-term asthma control with omalizumab, an anti-IgE monoclonal antibody in patients with severe allergic asthma. Poster (P417) presented at 15th European Respiratory Society Congress, Copenhagen, Denmark, 17-21 September 2005.
[2] Holt PG, Macaubas C, Stumbles PA, Sly PD. The role of allergy in the development of asthma. Nature 1999;402(Suppl.):B12 - 17.
[3] Chuchalin AG et al. Long-term safety and tolerability of omalizumab, an anti-IgE monoclonal antibody, in patients with severe allergic asthma. Poster (P421) presented at 15th European Respiratory Society Congress, Copenhagen, Denmark, 17-21 September 2005.
[4] Holgate S et al. Omalizumab significantly improves FEV1 in patients with severe persistent allergic asthma: a pooled analysis. Poster (P419) presented at 15th European Respiratory Society Congress, Copenhagen, Denmark, 17-21 September 2005.
[5] Beeh K-M et al. Omalizumab significantly improves quality of life in patients with severe persistent allergic asthma: a pooled analysis. Poster (P424) presented at 15th European Respiratory Society Congress, Copenhagen, Denmark, 17-21 September 2005.
[6] GINA. The Global Burden of Asthma Report 2004. http://www.ginasthma.com
[7] American Thoracic Society. Proceedings of the ATS workshop on refractory asthma. Current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med 2000; 162:2341-2351.
[8] World Health Organization. http://www.who.int/mediacentre/factsheets/fs206/en/
[9] Global Strategy for Asthma Management and Prevention 2004; 126-132. http://www.ginasthma.com
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