FDA guidance outlines that biosimilars may be approved based on pharmacokinetic (PK) and pharmacodynamic (PD) biomarker data in lieu of a comparative clinical study. While a close association between the biomarker and clinical outcome is not required, good understanding of the relationship can be informative. The current analyses assess the relationship between eosinophils and asthma exacerbations for two Interluken-5 (IL-5) antagonists: mepolizumab and reslizumab.  Individual-patient data from trials in subjects with severe eosinophilic asthma for these two approved products were analyzed. The treatment duration ranged 16 to 52 weeks in 5 trials where eosinophil and outcome data were collected at baseline and over the treatment duration. Traditional and extended random effects Cox proportional hazards models were used to evaluate whether eosinophil counts are prognostic factors for time-to-first and subsequent exacerbations. Covariates were included both as baseline and time-varying factors. The final analysis included data from 2,897 asthma patients. Treatment significantly reduced asthma exacerbation risk (mepolizumab pooled hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.47-0.61, reslizumab pooled HR 0.54, 95% CI 0.44-0.66). In untreated subjects, elevated baseline eosinophils were associated with increased exacerbation risk (pooled HR 1.2, 95% CI 1.0-1.4), but this was not true post treatment. Baseline eosinophils accounted for 13% of the mepolizumab and 10% of the reslizumab treatment effect. On the other hand, time-varying eosinophils accounted for 52% of the mepolizumab and 34% of the reslizumab treatment effect. While eosinophils would not meet expectations for use as a surrogate endpoint when approving new drugs, they are a prognostic factor for asthma exacerbations and can explain 34-52% of IL-5 agonist effects, lending credibility to eosinophils as a relevant biomarker for biosimilar development. 

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