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

Drug Metab Dispos

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.).

Published: May 2016

* The increasing development of ADCs has prompted pharmaceutical companies to investigate how they are absorbed, distributed, metabolized, and excreted (ADME) in the body.
* In 2014, an international working group was formed to address ADC ADME challenges and propose scientifically sound evaluation strategies, which are detailed in a white paper released by the group.

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.

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http://dx.doi.org/10.1124/dmd.115.068049	DOI Listing

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