Final FDA guidance on clinical pharmacology considerations for ADCs

The US Food and Drug Administration (FDA) has announced the availability of a final guidance for industry titled Clinical Pharmacology Considerations for Antibody-Drug Conjugates (ADCs), replacing the February 2022 draft guidance.

This final guidance provides recommendations to assist industry and other parties involved in the development of an antibody-drug conjugate (ADC) consisting of a cytotoxic small molecule drug or payload conjugated by a chemical linker to an antibody or antibody fragment.

The agency explained that ADCs combine the selectivity of an antibody for a specific target with the potency of a small-molecule drug. Selection of optimal dosing strategies for ADCs requires careful consideration of the pharmacokinetic and pharmacodynamic characteristics of the antibody and the payload because different constituent parts of the ADC can independently impact safety and/or efficacy. For example, a relatively small increase in the systemic exposure of the payload can cause significant adverse reactions that are dose limiting from a safety perspective.