• The US regulatory framework provides more streamlined pathways and incentives for drug repurposing compared to the EU and Japan.
• The EU and Japan have unique mechanisms, such as the adaptive pathways and Sakigake designation, that can be leveraged for repurposing.
• Regulatory harmonization and enhanced collaboration can accelerate drug repurposing for rare diseases globally.
• The study proposes actionable recommendations to improve regulatory frameworks and patient access to repurposed drugs.