Results of a clinical study showed 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.

Xolair also significantly improved patients' asthma-related quality of life.

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.
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.

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.

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 =0.5-point improvement ).
Add-on Xolair therapy produced significantly greater improvements than placebo for each individual AQLQ domain ( p<0.002 ) and overall score ( p<0.001 ).
In addition, a significantly greater proportion of patients receiving Xolair achieved a clinically meaningful =0.5-point improvement from baseline in their AQLQ score than patients receiving placebo ( 60.8% vs 47.8%, p=0.008 ).

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.

Source: 101st International Conference of the American Thoracic Society ( ATS ), 2005


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