Intra‐Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing

Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

“…We propose ITM as a novel methodology complementing and enhancing existing drug development approaches to accelerate development of NMEs and of existing drugs in vulnerable populations . The approach is uniquely positioned to address current translational research limitations.…”

“…The approach is uniquely positioned to address current translational research limitations. Our ITM concept manuscript discusses the many applications of the approach with detailed examples and applicable developmental scenarios …”

“…Safety concerns associated with new molecular entities (NMEs) lead to substantial preclinical developmental costs, delaying entry into first‐in‐human (FIH) testing. To help address these challenges we introduce a novel drug development approach, Intra‐Target Microdosing (ITM), combining features of “microdosing,” the systemic subpharmacological testing of drugs, and intra‐target drug delivery …”

Phase 0/microdosing approaches: time for mainstream application in drug development?

“…It is obviously of value to obtain, as soon as possible, data in the stage most likely to lead to termination of development. Other methodological advantages over phase I approaches discussed later are the ability to test multiple candidates simultaneously in the same individuals (cassette microdosing), the ability to test enteric drugs by administering them parenterally and the use of methods such as ITM 11,13,16,28 .…”

“…These advantages allow triaging of preclinical candidates for entry into clinical Adoption of phase 0/microdosing approaches by drug developers has been limited by uncertainty about the impact of non-linearity on extrapolation from subtherapeutic to therapeutic-level exposures, the perception that only pharmacokinetic data can be obtained with these approaches and the concern that application of phase 0 approaches will lead to delays in developmental timelines 26,27 . However, a range of research projects have since been conducted to optimize the effectiveness of extrapolation, expand the range of applications, including the study of pharmacodynamics, biomarkers and mechanism of action (MOA), and improve the versatility of strategic planning (for example, with the use of adaptive phase 0/phase I designs) [28][29][30][31][32][33][34][35] . Such efforts included the formation of consortia and networks dedicated to phase 0/microdosing approaches ( Table 2).…”