Editorial: Incorporating Phase 0 microdosing as a powerful tool into a new vision of drug development

Phase 0 microdosing—testing compounds at subtherapeutic doses in humans—enables early decisions in drug development with a reduced preclinical safety package. Its uptake has been slow despite advantages such as better decisions informed by early human data, reduced animal experiments, and access to vulnerable populations. Intratarget microdosing (ITM) enhances this approach by assessing safety or efficacy-related biomarkers beyond pharmacokinetics, including target expression via Positron Emission Tomography. The CIVO platform, an injectable device for surface-accessible tumors, can microdose up to eight drugs simultaneously and generate human pharmacodynamic data safely, improving translation over animal efficacy data.

Study at a glance

Abstract

Editorial on the Research Topic Incorporating Phase 0 microdosing as a powerful tool into a new vision of drug developmentPhase 0 microdosing, the testing of compounds at subtherapeutic doses in human to enable early decisions in drug discovery and development has been utilized for some years.The uptake was slow even though the concept is attractive and the pre-clinical safety package enabling first human testing is reduced (Burt et al., 2020).The attractiveness comes from the potential to facilitate better decisions informed by early human data, save animal experiments, obtain data in vulnerable populations, and increase the quality and value of subsequent studies at therapeutic doses.The new concept of intratarget microdosing (ITM) promises to enhance scope, value, and impact (Burt et al., 2017) increasing the appeal of Phase 0 studies.Technological developments, the importance of streamlining the drug development process to improve health at acceptable cost, and the increasing desire to reduce animal testing (Combes et al., 2003) give additional momentum.ITM has the capacity to assess safety or efficacy related biomarkers going beyond the earlier microdose focus on pharmacokinetics, and in combination with Positron Emission Tomography target expression or engagement related endpoints.Recently intratumoral ITM was tested as a tool for precision medicine in oncology (Peruzzi et al., 2023).As part of this Research Topic Gundle et al. describe a technology platform for intratumoral microdosing of oncology drugs called CIVO (clinical in vivo oncology) platform.The platform was designed to generate human PD data early at low risk for study participants and first described by Klinghoffer et al. (2015).CIVO is based on an injectable device that can be used for surface-accessible tumors and can microdose up to eight different drugs.Gundle et al. provide an overview of this device over the years, showing its successful use for several drugs over multiple clinical trials.The platform enables the direct access to human PD data in a safe and controlled way, a clear advantage over animal efficacy data that comes with the risk of poor translation.Based on the observed intra target responses of the candidate drugs it is possible to rule-in and