First humanized antibody for asthma targets IgE, an underlying cause of the disease
Basel, 23 June 2003 - Novartis announced today that the novel IgE-blocker Xolair® (Omalizumab) for Subcutaneous Use has been approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe persistent asthma in adults and adolescents. Xolair is the first humanized therapeutic antibody for the treatment of asthma and the first approved therapy designed to target the antibody IgE, a key underlying cause of the symptoms of asthma that has an allergic component. Xolair is expected to be available in the US by July 2003.
Xolair is indicated for adults and adolescents (12 years of age and above) 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. Xolair has been shown to decrease the incidence of asthma exacerbations in these patients. Safety and efficacy have not been established in other allergic conditions.
"We are delighted by this decision, which marks an important breakthrough for patients who are unable to control their asthma despite the wide range of therapies currently available," said Thomas Ebeling, Chief Executive Officer, Novartis Pharma AG. "Novartis and its collaborators are proud to have developed this innovative approach to tackling the growing problem of asthma, and we welcome the FDA's approval which allows us to turn this exciting scientific concept into a therapeutic reality for the benefit of patients and their families."
According to the National Institutes of Health, direct and indirect financial costs for all forms of asthma in the US totaled USD 14 billion in 1998. In addition, asthma leads to at least two million emergency room visits and more than 5000 deaths in the United States each year, according to the Center for Disease Control and Prevention's National Center for Health Statistics.
Xolair is being jointly developed under an agreement among Novartis Pharma AG, Genentech, Inc. and Tanox, Inc., and will be co-marketed in the United States by Genentech and Novartis Pharmaceuticals Corporation. In addition to approval in the United States, Xolair has also received marketing license from health authorities in Australia.
Clinical Study results
The companies' data submission to the FDA included two 52-week pivotal Phase III clinical trials with 1071 asthma patients, 12-76 years of age, as well as data from several supportive safety and efficacy studies, including the 1899-patient ALTO safety study. The pivotal trials were designed to study a reduction in asthma exacerbations. The co-primary endpoint of each study was the number of asthma exacerbations per patient during the stable-steroid phase and the steroid-reduction phase. Patients were randomized to receive subcutaneous Xolair or placebo every two or four weeks. Doses were determined based on patients' body weight and IgE level. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment (stable-steroid phase) and tapered during a further 12-week treatment period (steroid-reduction phase).
When used as an add-on therapy to inhaled corticosteroids, in both pivotal clinical trials, Xolair reduced mean asthma exacerbations ("asthma attacks") per patient by 33%-75% during the stable-steroid phase and 33%-50% during the steroid-reduction phase. Reduction in asthma exacerbations was confirmed by improvements in other measures of asthma control including asthma symptom scores such as nocturnal awakenings and daytime asthma symptoms.
Safety Information
Xolair has not been shown to alleviate asthma exacerbations acutely and should not be used for the treatment of acute bronchospasm or status asthmaticus. Xolair should not be abruptly substituted for systemic or inhaled corticosteroids. Decreases in corticosteroids should be performed only under the direct supervision of a physician and may need to be reduced gradually.
The most serious adverse reactions occurring in clinical studies with Xolair are malignancies (0.5% in Xolair vs 0.2% in placebo) and anaphylaxis (<0.1% in Xolair). The difference in malignancy between the Xolair and placebo arms was not statistically significant. Xolair treatment is generally well tolerated. The most frequent adverse events included injection site reactions (45%), viral infections (23%), upper respiratory tract infections (20%), sinusitis (16%), headache (15%), and pharyngitis (11%). These events were observed at similar rates in Xolair-treated patients and control patients.
About IgE and the Allergic Cascade
Asthma with an allergic component is a chronic inflammatory disorder of the airways, in which exposure to an aero-allergen triggers an allergic cascade that may result in airway inflammation and obstruction. In some patients, when allergens enter the body, IgE antibodies are produced and circulate in the blood. IgE circulating in the blood binds to mast cells, which contain the inflammatory chemicals (histamine, leukotrienes, others). Upon exposure to an allergen, IgE on the mast cell cross-links and triggers mast cells to release these chemicals. This chemical release triggers the inflammation, bronchial constriction and coughing associated with asthma. Xolair is designed to bind to the circulating IgE antibodies in the blood, decreasing the amount of IgE antibodies available to bind mast cells. With Xolair, fewer IgE antibodies can bind to mast cells, making IgE cross-linking less likely and inhibiting the mast cell's release of those chemicals that can lead to the symptoms of asthma.
This release contains certain "forward-looking statements", relating to the Group's business, which can be identified by the use of forward-looking terminology such as "is expected", "will be", or similar expressions, or express or implied discussions regarding potential future sales of existing products, potential new products or potential new indications for existing products, or by other discussions of strategy, plans or intentions. Such statements reflect the current views of the Group with respect to future events and are subject to certain risks, uncertainties and assumptions. There can be no guarantee that existing products will reach any particular sales levels, or that any new products will be approved for sale in any market, or that any new indications will be approved for existing products in any market. In particular, management's expectations could be affected by, among other things, new clinical data; unexpected clinical trial results; 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; and 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 described herein as anticipated, believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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