Overcoming Barriers to Off-Patent Drug Repurposing: A Lifecycle-Based Policy Solutions

Mario García Díaz^1,2*David Epstein³Jaime Espin^1,4,5

• ¹Escuela Andaluza de Salud Publica, Granada, Spain
• ²Universidad de Granada Facultad de Ciencias Economicas y Empresariales, Granada, Spain
• ³Universidad de Granada Departamento de Economia Aplicada, Granada, Spain
• ⁴Instituto de Investigacion Biosanitaria de Granada, Granada, Spain
• ⁵Centro de Investigacion Biomedica en Red, Madrid, Spain

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 real-world 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.