Overcoming barriers to off-patent drug repurposing: a lifecycle-based policy solutions García Díaz, Mario Epstein, David Mark Espín, Jaime Drug repurposing off-patent medicines Policy solutions Introduction: Drug repurposing leverages existing medicines to reduce time and costs for exploring new therapeutic indications. However, off-patent medicines do not provide enough private incentives for investment, and prescribing by active ingredient can be a major barrier. Academics and non-profit sponsors also face regulatory barriers. Methods: This study combined a structured literature review with a questionnaire completed by 25 drug repurposing experts to identify key challenges and policy solutions across the full lifecycle of off-patent drug repurposing. Results: Public funding is generally available for the early-stage research, where opportunities often arise from off-label uses and real-world evidence. However, limited support for confirmatory clinical trials, combined with the predominance of academics and non-profit sponsors lacking regulatory objectives, reduces the likelihood of successful authorisation to below 30%. Policy solutions include prioritising research into rare diseases and other conditions with unmet health needs, and call for a more prominent role of governments in public investment and in reinforcement of public–private partnerships. Substitution in community pharmacies remains a major challenge, which may be addressed through indication-based differentiation and enhanced dispensing controls. Some innovative public intervention mechanisms, such as Social Impact Bonds and the InterVentional PharmacoEconomics proposal, offer potential, although realworld experience is still limited. Conclusion: Off-patent drug repurposing faces persistent financial and regulatory barriers that require a central role from academics and non-profit sponsors, supported by governmental engagement throughout the lifecycle. Although steps have been taken in recent years, efforts remain insufficient, and structural and political barriers continue to hinder broader implementation. 2025-11-12T11:16:57Z 2025-11-12T11:16:57Z 2025-10-24 journal article Garcia-Diaz, M., Epstein, D., & Espin, J. (2025). Overcoming barriers to off-patent drug repurposing: a lifecycle-based policy solutions. Frontiers in Pharmacology, 16(1670845), 1670845. https://doi.org/10.3389/fphar.2025.1670845 https://hdl.handle.net/10481/107943 10.3389/fphar.2025.1670845 eng info:eu-repo/grantAgreement/H2020/101095593 http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Frontiers Media