Model-informed development of a cost-saving dosing regimen for enfortumab vedotin

Hoog, C.J.P.O.; Rieborn, A.; Moes, D.J.A.; Hendrikx, J.J.M.A.; Heijden, M.S. van der; Franken, M.D.; Hulle, T. van der; Kruchten, M. van; Willemsen, A.E.C.A.B.; Koolen, S.L.W.; Boerrigter, E.; Heine, R. ter

doi:doi:10.1007/s00280-025-04764-x

AimEnfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.MethodsPopulation pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to...Show moreAimEnfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.MethodsPopulation pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to the approved body weight-based dosing regimen was defined as conservative equivalent boundaries of 90-111% for the calculated geometric mean ratios (GMRs) of area under the concentration-time curve and trough concentration.ResultsA weight-band based dosing regimen for each dose level of enfortumab vedotin was developed. The GMRs for all pharmacokinetic outcomes were within the predefined equivalence boundaries. In addition, a more even exposure distribution was observed across the body weight quartiles. The average costs savings across all dose levels and per weight-band were approximately 15%.ConclusionThe proposed alternative dosing regimen shows that drug costs and spillage of enfortumab vedotin can be reduced while maintaining an equivalent and more evenly distributed exposure in treated patients.Show less

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Model-informed development of a cost-saving dosing regimen for enfortumab vedotin