Core insights – Developing an HTA framework to support value driven mechanism-based drug repurposing for patients, payers and society

The HTA transformation envisioned within the REPO4EU project is well underway, with clear progress and tangible achievements demonstrating that when HTA is prioritized early, the pathway to the patient becomes clearer.

Preliminary results of an early health economic evaluation have been generated to demonstrate the potential societal value of innovative drug repurposing in treatment-resistant hypertension. By utilizing headroom analysis and exploratory scenarios, we showcased exactly how early value assessments can steer development decisions. Furthermore, we have successfully integrated HTA considerations into the very heart of the REPO4EU clinical trials. By co-designing trial protocols for REPO-HYPERII, REPO-DIPG, and REPO-THYROID, we ensure that economic data and patient-based evidence are captured from day one, aligning our data collection with future regulatory requirements.

Experts in HTA, clinical medicine, pre-clinical research, as well as regulatory stakeholders contributed to this effort, with the aim of identifying challenges and opportunities in mechanism‑based drug repurposing that have subsequently informed the refinement of our framework.

Recognizing that innovation cannot thrive in isolation, REPO4EU has also hosted two landmark policy events in Brussels. These engagements have brought together representatives from the European Commission, HTA bodies, regulators, payers, and patient groups, and successfully initiated a substantive dialogue on how repurposed drugs can be effectively integrated into European reimbursement systems. Discussions examined how current HTA processes, pricing mechanisms, and reimbursement frameworks influence the feasibility, evidence requirements, and long-term accessibility of repurposed medicines, particularly for off-patent products and indications not expected to offer generation of substantial revenue. Participants emphasized the need for early alignment between clinical evidence generation, HTA expectations, and payer needs, as well as the critical role of patient-centered and fair access models in supporting sustainable drug repurposing across Europe.

Beyond meaningful dialogue and scientific publications, REPO4EU is developing the practical tools needed to translate this HTA transformation into a tangible, next‑day drug repurposing reality. Within our  platform, at the heart of the entire REPO4EU ecosystem, the first version of the HTA module is already available, and offers the following key features:

• Guidance and decision-support materials.
• A curated compendium of global HTA agencies, communities and guidelines.
• A ready-to-use health economic model template.
• The SMART Tool (Systematic Model adequacy Assessment and Reporting Tool).

Mechanism-based drug repurposing can deliver cost-effective, high-value treatments, particularly in areas of unmet medical need and rare diseases. Yet the novelty of mechanism-based and network pharmacology approaches presents inherent challenges: it generates potential drug combinations and indication pairs that need to be prioritized, often involving small patient populations, limited evidence, and high uncertainty.

This challenge has become the driving force of our work to develop an HTA framework that is structured, accessible, and practical, combining methods, guidance, and policy recommendations tailored to the unique nature of mechanism-based drug repurposing. Our goal is to empower researchers and developers, even those without prior HTA expertise, to utilize HTA methods in making informed decisions early, assess return on investment (ROI) at acceptable prices, and generate meaningful evidence that matters to patients, payers, and regulators.

Continuous engagement with multidisciplinary stakeholders remains essential to ensure the ongoing optimization of our HTA methodologies and the integration of emerging recommendations and regulatory insights. Moving from theory to practice, we are actively testing and refining our framework through real-world pilot studies within REPO4EU, ensuring its relevance across diverse repurposing scenarios.

By embedding HTA into the very DNA of the development lifecycle, we aim to reduce uncertainty, generate robust evidence and ultimately ensure that promising repurposed drugs reach the patients who need them most.

Our multidisciplinary HTA team is led by Maastricht University Medical Center (MUMC+), leveraging their deep-seated leadership in health economic evaluation and HTA methodology across a wide range of clinical areas. MUMC+ provides the strategic and scientific direction necessary to turn complex qualitative research into actionable early value assessments.

This effort is powered by a network of partners from within the REPO4EU Consortium (Maastricht University, Brigham and Women’s Hospital/Program on Regulation, Therapeutics, And Law (PORTAL), H.M. Pharma Consultancy, IPSIS PACTIS, University of Porto, 3D-PharmXchange), each bringing a vital piece to the puzzle: preclinical models prioritization, network medicine and systems’ biology, cross-sectional integration of technology assessment, legal advisory and regulatory strategies, research ethics and drug development programs.

By working in a unified ecosystem, the team ensures a seamless delivery of results, paving the way for a more efficient and patient-centered future in drug repurposing.