Future of AZ’s benralizumab lies in personalized medicine opportunity.
AstraZeneca/ MedImmune’s benralizumab caused a significant reduction in asthma exacerbation rates in patients with severe, uncontrolled asthma, according to data from a Phase IIb trial published in The Lancet Respiratory Medicine. However, its market opportunity may depend on a carefully specified patient population.
The Phase IIb dose-ranging, placebo-controlled study, conducted by MedImmune, met its primary endpoint of reduction in asthma exacerbation rate versus placebo over a period of one year.It also met secondary endpoints of patients experiencing improvements in lung function and asthma control as measured by the Asthma Control Questionnaire (ACQ-6).
While Datamonitor Healthcare believes the results are encouraging due to the observed improvements in asthma control and lung-function, the overall impact of biologics such as benralizumab on asthma treatment strategies should not be overstated. A key opinion leader interviewed by Datamonitor Healthcare doubts the potential of anti-IL-5 pipeline candidates, noting that there has been a minimal effect seen in a small subset of patients. This opinion echoes the Phase II data, where statistically significant effects were only observed in the subgroup analyses of patients with blood eosinophil levels ≥300 and ≥400 cells/microliter.
“With the anti-IL-5 drugs, there are a small number of patients that get an effect but the effect is not that great. So it is not like a magic effect, whereas Xolair is really effective in patients who respond. That is not the case with anti-IL-5 and certainly not the case with anti-IL-13.”
Carefully selected patient groups
Leonardo M Fabbri, in a commentary piece in the The Lancet Respiratory Medicine, said benralizumab, in the Phase IIb trial, not only reduced exacerbations (annual exacerbation rate 0.34 in benralizumab 100 mg group vs 0.57 in placebo group, difference 41%, 80% CI 11 to 60, p=0.096), but also improved lung function, asthma control, and quality of life— “effects that might be related to its more potent action as compared with anti-interleukin 5 in monoclonal antibodies.”
However, he noted that the study design took into account several preclinical and clinical studies into the effects of anti-IL-5 drugs in asthma, particularly regarding the careful selection of patients (all had well-documented eosinophilic, steroid-resistant asthma and a history of two to six exacerbations, all treated with steroids, in the previous year). “Clearly, this well-designed, complex Phase II study has provided important information to properly inform the design of a Phase III study,” Dr Fabbri wrote.
Overall though, Dr Fabbri believes targeted therapies with new anti-IL-5 or anti-IL5Rα drugs “seem very promising and safe for very selected patients with severe steroid-resistant asthma, and possibly some patients with COPD.” However, he added, “Their role in less selected patients with asthma or COPD will need additional clinical trials comparing their efficacy and safety with those of existing anti-inflammatory therapies.”
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Posted in Respiratory.