Repurposing Off-Patent Medicines: Insights from the EU Pilot Initiative

EU Pilot Initiative for Repurposing Off-Patent Medicines: Core Outcomes and Regulatory Support

Repurposing off-patent medicines offers a promising pathway to address unmet medical needs, particularly in rare diseases where commercial incentives are low. The European Medicines Agency (EMA) pilot project, launched in October 2021, facilitated this process by selecting nine projects from 40 submissions, primarily from academia. These focused on therapeutic areas like immunology, oncology, neurology, and nephrology, with most targeting rare diseases defined in the EU as conditions with a prevalence of ≤5 in 10,000 people. Key findings highlight the value of tailored scientific advice (SA) from the EMA and the Spanish Agency of Medicines and Medical Devices (AEMPS) in refining development plans, though involvement from marketing authorization holders (MAHs) remained limited, highlighting barriers in transitioning evidence to regulatory approval.

Tailored Regulatory Guidance for Academia

Customized regulatory support empowered not-for-profit organizations to generate evidence for new indications of off-patent drugs without pharmaceutical industry involvement. The pilot’s most impactful finding is the successful provision of this support, with six projects receiving EMA assistance and three supported by AEMPS. This included multiple rounds of feedback on briefing documents for SA procedures, which typically take about six months compared to the standard one-month timeline outside the pilot.

Specific examples from the selected cases illustrate this: in four projects without plans for new clinical studies, SA affirmed the sufficiency of existing data, such as over 30 years of off-label use or evidence aligned with therapeutic guidelines for severe rare diseases with limited options. In five early-stage projects planning phase II or III trials, SA provided critical recommendations on endpoint selection and patient criteria, where proposed primary endpoints were often deemed not clearly interpretable for clinical benefit or susceptible to variability from disease severity. These outcomes, show a predominance of clinical trial and real-world data submissions, reinforcing the pilot’s role in bridging academic research with regulatory pathways for conditions like neurological disorders in children, where real-world data supported planned registry or trial studies.

Economic and Incentive Boost for Rare Disease Access

The pilot’s findings demonstrate how regulatory support can accelerate access to repurposed medicines for rare diseases, potentially lowering development costs and timelines compared to de novo drug creation, which aligns with industry trends toward cost-effective innovation amid rising healthcare expenditures. For market access, pricing, and reimbursement, the limited MAH engagement—evident in only two successful collaborations, including one mediated by AEMPS leading to updated product information for iohexol in glomerular filtration rate determination. This highlights the need for incentives to encourage industry participation, as proposed in the EU pharmaceutical legislation reform allowing not-for-profit submissions directly to regulators.

This could enhance HEOR by prioritizing evidence from real-world and long-term off-label data, improving value assessments for payers in resource-constrained systems; for instance, affirming existing evidence without new trials in severe cases could streamline reimbursement for therapies with established safety profiles. This would ultimately benefit patient outcomes in underserved areas like pediatric neurology while informing future pilots to balance resource demands with tangible public health gains.