Rudolph, Bettina, Davis, John, Hainzl, Dominik and Walles, Markus (2024) A general perspective for the conduct of radiolabelled distribution, metabolism, and excretion studies for antibody-drug conjugates. Xenobiotica.

Abstract

Antibody-drug conjugates (ADCs) are a class of biopharmaceuticals that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxicity of small molecule drugs.
13 ADCs have been approved by regulatory authorities up to now, mainly for indications in oncology.
ADME (Absorption, Distribution, Metabolism, and Excretion) studies are essential for the development of small molecule drugs to evaluate their disposition properties. These studies help to determine the optimal dosing regimen and to identify potential safety concerns for the drug of interest in human. Distribution studies are also important as they help to determine the tissue distribution of the respective drug and its metabolites. This information is critical for understanding the efficacy and safety in preclinical and clinical studies.
For biologics, ADME studies are usually omitted. In this paper, we review the existing approval packages and literature for approved ADCs to see how often and to which extent ADME studies have been applied for registration.
We conclude that ADME studies are necessary for the development of ADCs if new linker and payloads are introduced to humans for the first time as these studies provide valuable information on the pharmacokinetic properties, optimal dosing regimen, and potential safety concerns. However, for the development of ADCs with established linker payload combinations, these studies are not deemed necessary if the distribution, metabolism and excretion properties have been described before.
Keywords: Distribution, Metabolism, Excretion; ADC, Payload, ADME, QWBA, SPECT/CT, AMS, CRDS

Item Type:	Article
Date Deposited:	26 Sep 2024 00:45
Last Modified:	26 Sep 2024 00:45
URI:	https://oak.novartis.com/id/eprint/52907