Mepolizumab’s therapeutic dosing and administration route were determined in the clinical development programme. The licensed mepolizumab dose and administration route is 100 mg s.c. every 4 weeks.1
The licensed dose of mepolizumab 100 mg s.c. was selected for phase 3 studies based on results from two clinical studies: a clinical pharmacology study MEA114092 and the dose ranging DREAM study.
MEA114092 evaluated the pharmacokinetic/pharmacodynamic response relationship of repeat mepolizumab doses i.v. or s.c. in patients with asthma and blood eosinophils >300 cells/µL.2
One of four doses was administered every 4 weeks:2
- 12.5 mg s.c.*
- 75 mg i.v.*
- 125 mg s.c.*
- 250 mg s.c.*
In all treatment groups, mepolizumab reduced blood eosinophil levels in a dose-dependent manner.2 The model determined that mepolizumab 75 mg mg i.v. was equivalent to 100 mg s.c., due to absolute s.c. bioavailability of approximately 75%.2 The study also facilitated a pharmacokinetic/pharmacodynamic model design to help inform dosing in Phase III studies in patients with severe refractory eosinophilic asthma.2
DREAM evaluated the efficacy, safety and pharmacodynamics of mepolizumab 75 mg i.v.,* 250 mg i.v.* and 750 mg i.v.* administered every 4 weeks to patients with severe refractory asthma.3 One of the study’s objectives was to help determine the optimum mepolizumab dose for further studies.3 Click here for more information on the DREAM study.
*This is an unlicensed dose/route of administration.
Mepolizumab’s dose schedule is based on its terminal half-life of approximately 20 days.1 Repeat dosing every 4 weeks provides approximately two-fold drug accumulation at steady state, with prolonged effects on blood eosinophil counts seen in a single dose.1
Pharmacokinetic and pharmacodynamic effects
Following s.c. dosing in patients with asthma, mepolizumab exhibited approximately dose-proportional pharmacokinetics over a dose range of 12.5–250 mg.1 The same dose every 4 weeks for 32 weeks reduced blood eosinophils from a geometric mean count at baseline of 290 to 40 cells/µL at Week 32 (N=182), a reduction of 84% compared with placebo.1 This magnitude of reduction was observed within 4 weeks of treatment.1 Mepolizumab absorption was found to be slow, with a median Tmax ranging from 4–8 days following s.c. administration to healthy subjects or patients with asthma.1
On the basis of predictive modelling from the MENSA study, mepolizumab was shown to be effective at reducing exacerbations irrespective of weight.4
▼This medical product is subject to additional monitoring.
- Nucala (Mepolizumab). Summary of product characteristics 2016.
- Pouliquen IJ, et al. Int J Clin Pharmacol Ther 2015; 53:1015–27.
- Pavord ID, et al. Lancet 2012; 380:651–9.
- Ortega HG, et al. N Engl J Med 2014; 371:1198–207.