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Page 12 of 15 Zanello et al. Rare Dis Orphan Drugs J 2023;2:9 https://dx.doi.org/10.20517/rdodj.2023.04

researchers, clinicians and pharmaceutical companies. In the European Union, the modification of the
Clinical Trials Regulation and the launch of the Clinical Trial Information System early in 2022 will
[30]
facilitate access to clinical trial data and ensure more transparency to the public .

Another area that would need more reflection is related to off-label use. Discrepancies are so striking
around the world that it is difficult to draw a single recommendation .
[25]
Some roadblocks to repurposing approaches do not require additional funding, but rather a better use of
already-available tools, incentives and initiatives, as well as a reflection on how to make the system more
efficient. For example, co-creation with patients is still not a reality in each and every therapeutic approach
and a fortiori in the examples that we saw in this study, despite lots of tools being already available . In
[31]
addition, new frameworks have been put in place by regulatory agencies, and the opportunities need to be
disseminated widely. Regulatory agencies are engaging with stakeholders in order to facilitate drug
repurposing. In 2019, the FDA, in collaboration with United States National Institute of Health (NIH) and
the Reagan-Udall Foundation, provided an overview of the challenges of drug repurposing while
encouraging further development [32,33] . In October 2021, the European Medicines Agency (EMA), in
collaboration with the Heads of Medicines Agencies (HMA), launched a pilot project to support the
repurposing of medicines by providing a piece of scientific advice for the selected repurposing candidate
[34]
projects .
Bringing repurposed medicines to rare disease patients offers a strong potential to address many unmet
needs. This approach, combined with the development of innovative clinical trial designs, can accelerate the
emergence of repurposed drugs targeting multiple rare diseases sharing the same molecular etiology. It
would also represent a valuable option for the so-called under-researched rare diseases for which unmet
needs must be urgently addressed. IRDiRC is tackling these questions with the Shared Molecular Etiologies
Underlying Multiple Rare Diseases Task Force and the Pluto Project [35,36] . Drug repurposing is clearly
recognized as an opportunity to accelerate the development of therapies for rare diseases and to address
Goal 2 of IRDiRC : “1000 new therapies for rare diseases will be approved, the majority of which will focus
[37]
[5]
on diseases without approved options”. The IRDiRC Task Force on Data Mining and Repurposing initially
addressed this topic by investigating the potential of biomedical data mining strategies to repurpose and
accelerate the development of drugs for rare disease patients. More recently, IRDiRC launched
[24]
the Drug Repurposing Guidebook Task Force with the objective of describing the tools, incentives,
resources and initiatives available to developers in the field. While the key principles of the Guidebook are
applicable to the case of repurposing, no specific repurposing building blocks were created at the time and
this will be the purpose of the creation of the “Drug repurposing Guidebook” module. This activity will
apply the key principles established for the Orphan Drug Development Guidebook Task Force and support
[23]
more efficient drug development plans.

In conclusion, drug repurposing represents a real opportunity to address unmet needs and improve
outcomes for rare disease patients. This IRDiRC Task Force has identified key factors for achieving
sustainable repurposing approaches in rare diseases, helping developers optimize their development
programs by determining the challenges and also opportunities associated with a particular drug
repurposing model or approach.

DECLARATIONS
Acknowledgments
The Task Force would like to thank the individuals and organisations (French Foundation for Rare