Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The Role of Academia in Driving Post-Approval Innovation in Areas of Unmet Medical Need ***

Dr. Martin Bommer (Abschlußjahr: 2020)

Summary
Language: English
Collaborations between clinical and basic researchers in academia and the pharmaceutical industry, have enabled the development of many of the medicines on the market today. But for many rare, complex or emerging diseases, where disease mechanisms may not yet be fully understood, or few development incentives exist, medical need for new treatments persists.   
A common approach is therefore to repurpose existing medicines to a new indication. The growth of predictive technologies that connect known drug targets to unresolved disease mechanisms will likely accelerate this trend. Academia is often at the forefront of hypothesis generation, and drug repurposing may offer a direct route to proof-of-principle clinical trials for a clinical researcher.
The present work seeks to understand how successful examples of academic drug repurposing were translated from idea through clinical research, to what extend academic clinical research contributes to regulatory approvals, and where the current marketing authorisation framework meets its limits.
The examples of investigator-initiated trials during the 2020 COVID-19 pandemic were explored. Early parallel publications and an EMA compassionate use opinion showed how researchers combined existing product knowledge and new indication-specific data to support clinical trials and proved/disproved the treatment hypotheses.
To understand contributions to MAs and extensions of indication, EPARs from paediatric and orphan MAs approved between 2015-2019 and orphan designation extensions of indication from 2001-2018, were searched for academic clinical trials that directly or indirectly contributed to such approvals. Two examples – propranolol in infantile haemangioma and treosulfan in stem-cell transplantation showed the clinicians’ role to initially prove the treatment hypothesis and to later collaborate with industry.   
Limits to repurposing of existing medicines and obtaining a new MA can be scientific or commercial. A lack of commercial incentives may lead to the dilemma of off-label use, where the scientific case is never comprehensively assessed. Recent regulatory initiatives aim to achieve SmPC or drug compendia updates based on academic clinical data in the absence of a viable commercial route.
Academic drug repurposing is likely to contribute to treatments in an increasing subset of unmet medical needs. The associated regulatory challenges for clinical trials and MAs are subject to many ongoing initiatives.
Pages: 65
Annexes: 1 Pages: 10