Bridging the gap between advanced therapy development and patient access in Europe: regulatory, clinical and translational challenges

Europe’s ambition to secure health sovereignty through global leadership in advanced therapies is now a central policy priority—both timely and achievable, and of clear strategic importance.

At the level of basic science and early clinical research, Europe is formidable. Its universities, hospitals, and research centres consistently generate high-quality data and pioneering therapeutic concepts. Many of today’s transformative ATMPs originate from publicly funded European science. Yet European patients frequently access these therapies later than their counterparts in the United States.

Some therapies do not reach Europe at all. This translational gap is not a single “valley of death,” but a series of misalignments along the translational pathway that slows, distorts, and ultimately limit access.

Unless Europe addresses the structural disconnect between discovery, development, regulation, and access, its ambitions (both economic and societal) will remain out of reach. Here are three of the most critical disconnections.

Beginning at the point of origin, there is a fundamental misalignment of incentives between early-stage developers—often academic or publicly funded—and downstream commercial actors. Academic innovators are rewarded for scientific novelty and early proof-of-concept, not for scalable development, regulatory optimisation, or evidence generation aligned with payer needs. On the other hand, industry has the knowhow to navigate the regulatory system and take the products to market. The necessary ‘handover’ after early development works well for chemical and biological medicines, but is not delivering for ATMPs. Their complexity and high uncertainty result in a discontinuity in development strategies, where promising therapies stall or are too expensive to be reshaped late in the process. This is especially evident in the case of some orphan therapies, where commercial returns are often limited or uncertain.

Second, fragmentation across the European system continues to undermine efficiency. Clinical trial approvals, manufacturing oversight (including Hospital Exemption), regulatory responsibilities and reimbursement decisions remain distributed across national and EU levels in ways that are not always coherent. Recent efforts to strengthen coordination and centralization in clinical trials and HTA are important and appreciated steps. However, their impact is gradual and, to date, relatively limited, while other regions continue to advance at a faster pace. Looking at the whole picture along the medicines life-cycle, variability in risk tolerance, administrative capacity, and clinical infrastructure further compound the disconnection. 

Finally,

European health systems cannot sustain the high prices required to generate adequate returns for industry without jeopardising their long-term financial stability.

This tension sits at odds with one of Europe’s defining principles: equitable and universal access to care, and results in development priorities being too often shaped by expected financial returns rather than unmet clinical need. Compounding this, much of the foundational science behind ATMPs is publicly funded, creating a legitimate concern that society pays twice: first for the research, and again for the final product at premium prices. 

The proposed changes in EU legislation and the Biotech Act acknowledge many of these challenges and signals a shift towards a more strategic, innovation-friendly framework. Its emphasis on expedited pathways, regulatory flexibility, and strengthened coordination is directionally correct, and very welcomed. However, the real question is not whether the legislation is well-intentioned, but whether it is sufficiently ambitious in practice. Incremental adjustments are unlikely to close the gap, and the pace of implementation risks lagging far behind the speed at which the science—and global competitors—are moving. 

The benefits that innovative therapies bring to European patients and to the economy are not in question. But legislation can do only so much, what is required is a more radical integration.

Take affordability as a case in point. While outcome-based payment models and risk-sharing agreements offer partial remedies, they do not address the underlying challenge: the distribution of value and risk across the system. Correcting this imbalance will require more assertive policy action, including fairer value-sharing mechanisms and a more strategic use of Europe’s collective purchasing power to support sustainable and equitable access. Greater transparency around R&D contributions, alongside the exploration of public or not-for-profit manufacturing models, could further strengthen this approach.

A less discussed issue is the allocation of regulatory resources. The current model relies heavily on national competent authorities contributing to centralised EMA procedures, often without clear alignment of incentives or accountability. This can lead to inefficiencies and variable quality in assessments. For highly specialised products such as ATMPs, a more centralised model—prioritising scientific expertise over national representation—would improve consistency and speed. 

Europe does not lack the expertise, ingenuity, or ambition to lead in advanced therapies, but it needs the coherence to deploy them effectively. The Biotech Act offers an opportunity to move beyond incremental reform towards a genuinely integrated system. This will require difficult choices: greater centralisation where it adds value, alignment of incentives from early stages, and a willingness to experiment with new regulatory and economic models. ATMPs, as the frontier of biomedical innovation, are the ideal testbed for a more flexible, responsive, and integrated regulatory ecosystem. We are choosing between relevance and decline.

Ana Hidalgo-Simon, Leiden University Medical Center, NL & reNEW (NNF21CC0073729)