Treatment of acute exacerbation of asthma and reduction of likelihood of hospitalization of patients suffering therefrom

Abstract

The invention provides a method of improving one or more clinical outcomes of an individual experiencing an acute respiratory attack. The acute respiratory attack may include acute reversible bronchospasm, severe acute bronchospasm, or acute exacerbation of asthma. The method includes administering to an individual suffering from an acute respiratory attack an effective amount of bedoradrine or a pharmaceutically acceptable salt thereof in combination with a standard of care (SOC) treatment regimen.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS[0001]This application claims priority from U.S. Provisional Application Nos. 61 / 262,352 and 61 / 392,917, filed Nov. 18, 2009 and Oct. 13, 2010, respectively, and incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]This invention relates to a method of treating severe episodes of asthma, preventing the manifestations of severe and long-lasting episodes of asthma from worsening, and reducing the likelihood of hospitalization (or other adverse clinical outcomes) of patients suffering from severe and long-lasting episodes of asthma, including without limitation, acute exacerbation of asthma. In particular, this therapeutic approach with MN-221 (generic name: bedoradrine) provides additional bronchodilation and improved clinical outcomes including reduced hospitalization when used adjunctively to (that is, in combination with) recognized standard respiratory care for acute asthma exacerbations (i.e., nebulized albut...

AI Technical Summary

Benefits of technology

[0009]Provided herein are methods for pharmacologically treating severe and long-lasting episodes of asthma, by providing intravenous administration of a highly β2-selective adrenoceptor agonist in conjunction with a standard of care treatment regimen and thus preventing the manifestations of severe and long-lasting episodes of asthma from worsening, and reducing the likelihood of hospitalization of patients suffering from severe and long-lasting episodes of asthma, including without limitation, acute exacerbation of asthma. Also provided herein are methods for selecting patients that are likely or unlikely to undergo such treatment.

[0010]In one aspect, the present invention provides a method of treating AEA, comprising administering an effective amount of the Active Agent to a patient in need of such treatment. In certain other aspects and embodiments, the invention also provides novel methods of reducing the likelihood of hospitalization (e.g., a reduced hospitalization rate or a reduced stay in an intensive care unit) and / or worsening of one or more manifestations of AEA in a patient suffering from AEA comprising administering an effective amount of the Active Agent to such patient. In other aspects, other methods of the present invention comprise determining that a patient is suffering from a long-lasting and severe asthma episode that is not responsive to initial standard of care treatment and administering to the patient an effective amount of the Active Agent. In a preferred embodiment, the Active Agent is administered parenterally, more preferably, intravenously.

[0012]In another aspect, the present invention provides a method of treating AEA by administering an effective amount of the Active Agent to a patient in need of such treatment wherein the AEA or one or more manifestations of the AEA are non-responsive or substantially non-responsive to treatment with SOC. In another aspect, the present invention provides a method of treating a severe and long-lasting episode of asthma by administering an effective amount of the Active Agent to a patient in need of such treatment, wherein the severe and long-lasting episode of asthma or one or more manifestations of it are non-responsive or substantially non-responsive to treatment with SOC. Within the aspects and embodiments of the present invention, in one embodiment, the Active Agent administered is MN-221 or pharmaceutically acceptable salts thereof. For example and without limitation, patients suffering from AEA (for example, those admitted to an emergency room because of an acute exacerbation of asthma), who were not responsive to SOC, were treated with MN-221 (in addition to having been treated with SOC) and their treatment outcomes compared with those of similar patients treated with SOC only (or SOC plus a placebo). The hospitalization rate among those patients who were treated with SOC only, was 54 percent (7 of 13, roughly half), compared to a hospitalization rate of 25 percent (4 of 16, roughly a quarter) among those patients who were treated with MN-221 and with SOC, demonstrating improved breathing ability (see, FIG. 1) and about a 50 percent reduction in hospitalization rate among AEA patients who were also treated with MN-221. Thus, the invention also provides novel methods of reducing the likelihood of hospitalization of patients suffering from AEA, who are non-responsive to SOC. In one embodiment of the invention, the likelihood of hospitalization of a patient suffering from an acute exacerbation of asthma treated with MN-221 alone or in combination with SOC falls to substantially less than half or fifty percent, preferably, to about a quarter (or twenty-five percent) of all patients suffering from an acute respiratory attack.

Problems solved by technology

Moreover, these treatments may not produce a significant clinical benefit and / or may provoke unwanted cardiovascular side-effects (e.g., tachycardia) when added to SOC.

Thorax (1988) 43:19-23) to provide some breathing benefit without undue side effects, such parenteral beta-agonist therapy has proven over the years to be too risky—especially from a cardiovascular liability standpoint—for limited observed benefit.

(2005) 6:142-7 showed that terbutaline added to SOC in children with status asthmaticus did not provide a significant improvement in clinical asthma score or ICU stay.

Moreover, the clinical benefit appears questionable, while the potential clinical risks are obvious.

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