Another rung on the Asthma ladder

Asthma
Another rung on the Asthma ladder
By Novartis, May 29, 2005 - 4:25:38 PM

Results of a clinical study presented at a leading international medical congress show that Xolair® (omalizumab) halved the rate of severe asthma exacerbations and reduced the rate of hospital emergency visits by 44% in patients with inadequately controlled severe persistent asthma, who are at high risk of life-threatening attacks.1 Xolair also significantly improved patients' asthma-related quality of life, according to data from the same study presented at the centenary congress of the American Thoracic Society this week.

Xolair is a first-in-class therapy that is given by injection every two or four weeks and blocks the action of IgE, the antibody responsible for triggering the cascade of allergic symptoms in patients with diseases such as allergic asthma. It offers a novel therapeutic approach to the control of asthma symptoms such as wheezing and shortness of breath, even in the most difficult-to-treat patients whose condition remains poorly-controlled despite receiving the best available therapy.

A total of 419 such patients, aged 12-75, were recruited for a double-blind, placebo-controlled, parallel-group, multicenter study called INNOVATE to assess the effect of add-on Xolair therapy on the rate of severe asthma exacerbations and emergency visits.1 The participants all had reduced lung function and a recent history of clinically significant exacerbations, despite receiving step 4 therapy as defined in the GINA guidelines, including high-dose inhaled corticosteroids, long-acting beta2-agonists and other controller medication (including oral corticosteroids) if required.

Severe exacerbations halved
The severe exacerbation rate (i.e. where lung function measured by PEF or FEV1 was less than 60% of personal best, requiring systemic corticosteroids) and the rate of emergency visits (i.e. hospital admissions, emergency room visits and unscheduled doctor's visits) were calculated during the treatment phase. Results showed that add-on Xolair therapy significantly reduced both the severe exacerbation rate (0.24 vs 0.48, p=0.002) and emergency visit rate (0.24 vs 0.43, p=0.038) compared with placebo. The authors concluded: "Omalizumab should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy."

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.

Around 300 million people in the world have asthma,4 of whom an estimated 15 million suffer from severe persistent disease.5 Their health and quality of daily life are severely affected, and asthma is estimated to cause more than 180,000 deaths worldwide each year.Until now there have been few additional therapeutic options available for these patients.

A further analysis of data from the INNOVATE study evaluated the impact of Xolair treatment on patients' quality of life, measured by the Asthma QoL Questionnaire (AQLQ) (i.e. individual domains, overall score and clinically meaningful more than or equal to0.5-point improvement).2 Add-on Xolair therapy produced significantly greater improvements than placebo for each individual AQLQ domain (p0.002) and overall score (p less than 0.001). In addition, a significantly greater proportion of patients receiving Xolair achieved a clinically meaningful more than or equal to 0.5-point improvement from baseline in their AQLQ score than patients receiving placebo (60.8% vs 47.8%, p=0.008).

Well-tolerated in children
Another study presented at the ATS congress evaluated the long-term safety and tolerability of Xolair in children aged 6-12 years at entry, who were eligible to join a three-year multicenter, open-label extension on completion of a one-year clinical trial (28-week double-blind core trial and 24-week open-label extension).

The percentage of patients who experienced adverse events (AEs) in the core trial was similar in the Xolair and placebo groups (89.3%, n=201 and 87.2%, n=95 respectively). Of the 309 patients who entered the 24-week extension of the core trial, 244 (79.0%) experienced an AE. A total of 188 patients continued into the three-year extension, of whom 103 completed the study. Of the 85 patients who discontinued, the majority withdrew consent due to study duration and maintaining study commitments.

Xolair was generally well-tolerated and most AEs were mild to moderate in severity. When evaluated by 28-week increments, the incidence of AEs was generally comparable or lower than that seen in the 28-week core trial. No AEs suggestive of immunological reactions were reported. Overall, there were 13 AEs that investigators suspected were drug-related. There were eight serious AEs of which only one (dyspnea) was considered to be drug-related. No evidence of clinically significant changes in vital signs, spirometry or laboratory parameters, including platelets, were observed following Xolair treatment.

Xolair was launched in the US in July 2003, and is also approved in Australia, Brazil, Canada, Dominican Republic, Guatemala, Israel, New Zealand and Venezuela. It has been developed under an agreement between Novartis Pharma AG, Genentech, Inc., and Tanox, Inc. The European Medicines Agency (EMEA) is due to announce its decision on Xolair approval later this year.

The foregoing release contains certain forward-looking statements that can be identified by terminology such as "could fulfill," "should be considered," "is due 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

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