Individualized dosing of evinacumab is predicted to yield reductions in drug expenses

Abstract

Background: Evinacumab is a first-in-class inhibitor of angiopoietin-like protein 3 (ANGPTL3) for treatment of the rare disease homozygous familial hypercholesterolemia (HoFH). With projected drug costs of $450,000 per person per year, the question rises if cost-efficacy of evinacumab can be further improved.

Objectives: To develop an individualized dosing regimen te reduce drug expenses.

Methods: Using the clinical and pharmacological data as provided by the license holder, we developed an alternative dosing regimen in silico based on the principles of reduction of wastage by dosing based on weight bands rather than a linear milligram per kilogram body weight (mg/kg) dosing regimen, as well as dose individualization guided by low density lipoprotein cholesterol (LDL-C) response.

Results: We found that the average quantity of drug used for a dose could be reduced by 34% without predicted loss in efficacy (LDL-C reduction 24 weeks after treatment initiation).

Conclusion: Dose reductions without compromising efficacy seem feasible. We call for implementation and prospective evaluation of this strategy to reduce treatment costs of HoFH.

Keywords: Cholesterol; Cost reduction; Dose individualization; Dose reduction; Evinacumab; Familial hypercholesterolemia; Pharmacodynamics; Pharmacokinetics.