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.

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 ).

" These results confirm that Omalizumab potentially provides an important breakthrough in the fight against allergic asthma," said 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 ).
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 ) 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.

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 an equal or greater than 200mL decrease. In the control group, 26.4% had a greater-than-or-equal 200mL increase in FEV1 and 26.1% had a greater-than-or-equal 200mL decrease. This equates to a net benefit of 11.6% for Xolair patients versus 0.3% for control ( P<0.0001 .

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 ).

Source: Novartis, 2005


XagenaMedicine2005