How Did Researchers Miss Asthma Drug's Potential?

NOVEMBER 09, 2016
Kenneth Bender
One year after the November 2015 FDA approval of mepolizumab (Nucala, GlaxoSmithKline) to treat severe asthma with eosinophilic phenotype, a review considers how initial studies missed its effectiveness, the subsequent evidence that supported its utility, and possible future applications.
 
The review was published in the November issue of Therapeutic Advances in Chronic Disease, with lead author Francesco Menzella, MD, Department of CardioThoracicVascular and Intensive Care Medicine, Pneumology Unit, IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Arcispedale Santa Maria Nuova Hospital, Reggio Emilia, Italy.  Mepolizumab for Severe Refractory Eosinophilic Asthma: Evidence to Date and Clinical Potential
 
"Early studies did not show a significant improvement in lung function, probably due to lack of efficacy in removing tissue eosinophils and pro-inflammatory cytokines," Menzella and colleagues observed.
 
The eosinophilic phenotype, identified in studies published in 2014, described the subgroup of patients most responsive to mepolizumab actions, particularly the countering of interleukin IL-5.  
 
Asthmatic patients with eosinophilic inflammation characteristically have a thickening of the basement membrane in the airway mucosa and are generally responsive to corticosteriods, Menzella and colleagues explain.  The anti- IL-5 effects of mepolizumab in these patients interfere with eosinophil recruitment and survival in the airways and granule maturation.
 
After identifying the patients most likely to benefit, two randomized controlled trials served to support the application for treating patients with severe eosinophilic asthma.  Menzella and colleagues anticipate further research on specific biomarkers for treatment-responsive subphenotypes.  In addition, they note that the FDA has required two post-marketing studies in children six to 11 years of age to help ascertain optimal dosage and duration of treatment.
 
Menzella and colleagues identify additional areas of investigation which may expand the indications for this and other anti-IL-5 agents.  These include chronic eosinophilic pneumonia (CEP) and a subgroup of patients with chronic obstructive pulmonary disease (COPD) demonstrating an eosinophil-predominant phenotype--recently termed by  researchers as Asthma-COPD Overlap Syndrome (ACOS).
 
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