Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper

Eugenia Kraynov; Amrita V Kamath; Markus Walles; Edit Tarcsa; Antoine Deslandes; Ramaswamy A Iyer; Amita Datta-Mannan; Priya Sriraman; Michaela Bairlein; Johnny J Yang; Matthew Barfield; Guangqing Xiao; Enrique Escandon; Weirong Wang; Dan A Rock; Nagendra V Chemuturi; David J Moore

doi:10.1124/dmd.115.068049

Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper

Drug Metab Dispos. 2016 May;44(5):617-23. doi: 10.1124/dmd.115.068049. Epub 2015 Dec 15.

Authors

Eugenia Kraynov¹, Amrita V Kamath², Markus Walles², Edit Tarcsa², Antoine Deslandes², Ramaswamy A Iyer², Amita Datta-Mannan², Priya Sriraman², Michaela Bairlein², Johnny J Yang², Matthew Barfield², Guangqing Xiao², Enrique Escandon², Weirong Wang², Dan A Rock², Nagendra V Chemuturi², David J Moore²

Affiliations

¹ Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., La Jolla, California (E.K.); Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, South San Francisco, California (A.V.K.); Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma, Basel, Switzerland (M.W.); Drug Metabolism, Pharmacokinetics, and Bioanalysis Department, AbbVie, Worcester, Massachusetts (E.T.); Disposition, Safety and Animal Research, Sanofi, Vitry sur Seine, France (A.D.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, New Jersey (R.A.I.); Departments of Drug Disposition, Development, and Commercialization, Eli Lilly and Co., Indianapolis, Indiana (A.D.-M.); Drug Metabolism and Pharmacokinetics, Celgene Corp., Summit, New Jersey (P.S.); Drug Metabolism and Pharmacokinetics, Bayer Pharma AG, Wuppertal, Germany (Mi.B.); Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Boston, Massachusetts (J.J.Y.); Bioanalytical Science and Toxicokinetics, Drug Metabolism and Pharmacokinetics, GlaxoSmithKline R&D, Ware, United Kingdom (Ma.B.); Preclinical Pharmacokinetics and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Biologics Discovery Drug Metabolism and Pharmacokinetics and Bioanalytics Department, Merck Research Laboratories, Palo Alto, California (E.E.); Biologics Clinical Pharmacology, Janssen R&D, Spring House, Pennsylvania, (W.W.); Amgen Pharmacokinetics and Drug Metabolism, Thousand Oaks, California (D.A.R.); Seattle Genetics Inc., Seattle, Washington (N.V.C); and Department of Pharmaceutical Sciences, Roche Innovation Center, New York City, New York (D.J.M.) eugenia.kraynov@pfizer.com.
² Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., La Jolla, California (E.K.); Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, South San Francisco, California (A.V.K.); Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma, Basel, Switzerland (M.W.); Drug Metabolism, Pharmacokinetics, and Bioanalysis Department, AbbVie, Worcester, Massachusetts (E.T.); Disposition, Safety and Animal Research, Sanofi, Vitry sur Seine, France (A.D.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, New Jersey (R.A.I.); Departments of Drug Disposition, Development, and Commercialization, Eli Lilly and Co., Indianapolis, Indiana (A.D.-M.); Drug Metabolism and Pharmacokinetics, Celgene Corp., Summit, New Jersey (P.S.); Drug Metabolism and Pharmacokinetics, Bayer Pharma AG, Wuppertal, Germany (Mi.B.); Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Boston, Massachusetts (J.J.Y.); Bioanalytical Science and Toxicokinetics, Drug Metabolism and Pharmacokinetics, GlaxoSmithKline R&D, Ware, United Kingdom (Ma.B.); Preclinical Pharmacokinetics and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Biologics Discovery Drug Metabolism and Pharmacokinetics and Bioanalytics Department, Merck Research Laboratories, Palo Alto, California (E.E.); Biologics Clinical Pharmacology, Janssen R&D, Spring House, Pennsylvania, (W.W.); Amgen Pharmacokinetics and Drug Metabolism, Thousand Oaks, California (D.A.R.); Seattle Genetics Inc., Seattle, Washington (N.V.C); and Department of Pharmaceutical Sciences, Roche Innovation Center, New York City, New York (D.J.M.).

PMID: 26669328
DOI: 10.1124/dmd.115.068049

Abstract

An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs.

Publication types

Review

MeSH terms

Animals
Antibodies, Monoclonal / metabolism*
Drug Industry / methods
Humans
Immunoconjugates / metabolism*
Pharmaceutical Preparations / metabolism*

Substances

Antibodies, Monoclonal
Immunoconjugates
Pharmaceutical Preparations