The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial

Abstract

This study compared the pharmacokinetic (PK) profile of a new liquid formulation of mepolizumab with the established lyophilized formulation. In this open‐label, parallel‐group, single‐dose study (NCT03014674; GSK ID: 204958), healthy participants were randomized (1:1:1) to receive a single mepolizumab dose (100 mg) administered subcutaneously as liquid in a single‐use prefilled syringe or single‐use prefilled autoinjector, or as a lyophilized formulation. Maximum plasma concentration, area under the plasma concentration–time curve from time zero (predose) to time of last quantifiable concentration (AUC0–t), and AUC from time zero to infinity (AUC0–∞) as well as additional PK parameters, safety assessments, and blood eosinophil count were evaluated. In total, 244 participants received study drug. All PK parameters were similar across the 3 groups; 90% confidence intervals for maximum plasma concentration, AUC0–t, and AUC0–∞ treatment ratios (liquid prefilled syringe or autoinjector vs lyophilized formulation) were within conventional bioequivalence bounds (0.80‐1.25), demonstrating statistical PK comparability. On‐treatment adverse event incidence was 29% to 38%. Mepolizumab liquid formulation administered via prefilled syringe or autoinjector had similar PK properties to the lyophilized formulation, with no safety concerns identified.

Extension of mepolizumab injection intervals as potential of saving costs in well controlled patients with severe eosinophilic asthma

“…Similar results were obtained in a study comparing the pharmacokinetic of the newly available liquid formula used in autoinjectors against the initially developed lyophilized formulation. 19 Both formulas shared similar pharmacokinetic profiles without significant differences, providing authenticity for our study where both options of therapy were used. On day 57 and 85 (approximately 8 and 12 weeks) after drug injection, blood eosinophils still were declined 50–60% compared to baseline and plasma concentrations of mepolizumab were measurable.…”

Targeting IL‐5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab

“…Such a condition can be translated to asthmatic patients before the next dose administration of a monoclonal antibody. Accordingly with pharmacokinetic studies in healthy subjects (Martin et al, 2019;Shabbir et al, 2019) that received approved doses of monoclonal antibodies (European Medicines Agency, 2015US Food andDrug Administration, 2015, 2017), while the maximum plasma concentrations of benralizumab and mepolizumab were '3 and '12 μg/ml −1 , respectively, the trough concentrations were '1 and '5 μg/ml −1 , respectively. Indeed, our results indicate that at these concentrations both the agents are effective in submaximally inhibiting the airway hyperresponsiveness to histamine in isolated airways.…”

Taking a Breather: Advances in Interleukin 5 Inhibition for Asthma Relief

“… Clinical trial history of Mepolizumab. Created with (accessed on 15 August 2022) [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. …”