Pharmacokinetic implications of dosing emicizumab based on vial size: A simulation study

Abstract

Introduction Emicizumab is dosed as mg/kg and, according to the label, any unused drug left in the vial(s) must be discarded, thereby wasting expensive resources. The aim of this study was to use population pharmacokinetics to illustrate the implications of changing the dosing interval to avoid wastage. Methods We used a previously published emicizumab PopPK model after extending its validation to children. We simulated PK parameters for labelled dosing regimens and for regimens using full vials with infusion frequency varied to keep the steady‐state drug concentration unchanged. Cost and drug savings were calculated. Results The model evaluation was successful. When rounding up, the average individual below 53, 47 and 39 has a time‐to‐trough increase of up to 5.7, 7.9 and 5.8 days for the QW, Q2 W and Q4 W regimen, respectively. This resulted in an annual cost reduction of up to $173,136, $75,747 and $61,319 USD per patient. At higher body weights, rounding down the dose to the nearest vial resulted in negligible changes in the steady state concentration and cost savings of up to $93,781, $46,891 and $23,446 USD per patient, respectively. Conclusion Individuals with a lower body weight may benefit from increasing dose intervals and rounding up dose up to the nearest vial, and individuals with a higher body weight from maintaining the injection frequency and rounding dose down to the nearest vial without significant change in emicizumab levels. Administering the entire vial may result in a reduction of vials used annually and potential cost savings.

Emicizumab state‐of‐the‐art update

“…The tool called Calibra® is freely available at http://Calibra.app and includes a patient module, myCalibra®, available on the Apple and Google applications stores. The scientific base for Calibra®’s set of functionalities has been previously published 41,47 . In essence, as shown in Figure 3, Calibra® allows the treating physician to input the patient weight and select the intended treatment regimen.…”

Prophylaxis in children with haemophilia in an evolving treatment landscape

“…Both studies used Monte Carlo simulations and concluded that rounding the dose is possible and results in cost savings. 48,49 One study refers to an online resource that can help identify the optimum dose 48 ;…”

“…Two recent studies examined rounding the emicizumab dose to whole vials. Both studies used Monte Carlo simulations and concluded that rounding the dose is possible and results in cost savings 48,49 . One study refers to an online resource that can help identify the optimum dose 48 ; the other suggests an alternative dosing regimen based on vial size and injection interval 49 …”

Emicizumab dose capping in obese patients with Haemophilia A: Early outcomes at a single centre

“…10 In a simulation study on the pharmacokinetic implications of dosing emicizumab based on vial size, the authors mention that emicizumab dose may be calculated based on ideal weight in obese patients, in analogy to factor VIII replacement therapy, where ideal weight may be the adequate reference for dose calculation. 11,12 The latter is due to the relatively small increase in plasma volume in relation to adipose tissue with increasing body weight and thus an increased in vivo recovery of FVIII in obese patients. Dosing based on ideal weight may avoid overtreatment of patients and would also be more beneficial from an economic point of view.…”

“…Dosing based on ideal weight may avoid overtreatment of patients and would also be more beneficial from an economic point of view. 11 In our view, in the case of emicizumab, dose adaptation should also aim to reduce the number of subcutaneous injections per administration to reduce the "injection burden" associated with treatment and, in theory, improve treatment adherence.…”