Rare Disease Moonshot’s contribution to the Consultation on the next Multiannual Financial Framework

Introduction

The Rare Disease Moonshot is a multi-stakeholder initiative uniting public and private actors, researchers, clinicians, patients, and funders to advance research and care for the 30 million people living with rare diseases in the EU. Rare diseases are not marginal - they are emblematic of the broader challenges facing Europe's innovation system: high unmet need, limited commercial incentives, fragmented infrastructure, and cross-border complexity.

We support the European Commission's ambition to make the EU a global leader in competitiveness and strategic autonomy. We believe that rare disease research is a strategic investment area that not only addresses vulnerable populations but also acts as a catalyst for high-risk, high-reward innovation that can strengthen Europe’s health resilience and global positioning.

Why the MFF architecture matters?

The structure of the MFF is more than a budgeting exercise-it determines what is visible, what is funded, and how impact is enabled. The potential merger of multiple programs (e.g., Horizon Europe, EU4Health, and health preparedness instruments) into a single Competitiveness Fund raises key concerns about visibility, accessibility, and strategic continuity.

Rare diseases require dedicated, flexible, and sustained investment approaches. A single consolidated fund may appear efficient on paper but risks flattening the complexity of needs into generalized calls that overlook niche or high-risk areas. Without clear mechanisms to preserve mission-oriented focus and equitable access, rare diseases could be sidelined.

Core principles for an inclusive and impactful MFF

End-to-End research continuity

The future MFF should enable the seamless progression of promising innovations across the full spectrum of research and innovation activities-from discovery to implementation-through a responsive, purpose-driven funding architecture. A "Fund Forward" model is proposed to operationalize this approach. This model assumes the existence of complementary programmes, such as the European Research Council (ERC)-which funds investigator-driven frontier research-and the European Innovation Council (EIC), which supports the scale-up of breakthrough innovations, particularly by startups and SMEs. Each serves distinct but sequential purposes in the innovation chain. The ERC enables high-risk scientific discovery, while the EIC helps move validated concepts toward market or system uptake. Ensuring coordinated transitions between these instruments is essential to maximize their impact, especially in high-need areas like rare diseases. Under this model, strategic research assets, infrastructures, or consortia would be able to move flexibly between programmes-such as from frontier science funded through the ERC, to collaborative projects supported under Pillar II, through to scale-up activities under the EIC or health system deployment supported by EU4Health-without encountering artificial administrative or programmatic barriers.

Continuity across these stages is currently one of the weakest links in the EU's research funding landscape. Valuable research outcomes too often stall when transitioning from lab-based discovery to applied development, largely due to fragmented programme eligibility, discontinuities in timelines, or mismatched priorities between funding streams. These structural inefficiencies disproportionately affect high-need, low-commercial-return areas like rare diseases, where the pathway to implementation is long, complex, and highly dependent on public investment. In this context, FP10 should adopt follow-up funding mechanisms that allow for iterative cycles of research and development-where early clinical findings can inform new discovery phases. This would accommodate the non-linear nature of rare disease innovation, where translational steps often require revisiting upstream science to refine mechanisms or develop biomarkers. In other words, to unlock the full value of EU investments, stronger programmatic connectivity between research-focused instruments (e.g., FP10) and deployment-oriented programmes (e.g., EU4Health) is essential. A "pipeline logic" embedded within the MFF would support a more dynamic, lifecycle-based portfolio management system. It would enable innovations-especially those emerging from high-risk domains-to be tracked and supported through maturity, with progress-based funding decisions rather than application-based resets. This would reduce inefficiencies, enable better planning for infrastructures and partnerships, and ensure that promising innovations can reach patients more efficiently. In the rare disease field, where innovations often span multiple cycles of funding and take years to reach clinical utility, such a model would significantly improve predictability and strategic alignment across the ecosystem.

Dedicated streams for strategic areas

Even within a consolidated Competitiveness Fund, there must be clear and visible lines of funding for under-represented and high-need areas like rare diseases. Current fragmentation in eligibility criteria already hinders coordination. Without earmarked streams or integrated calls with rare disease eligibility, these topics risk being lost to more commercially attractive domains. Calls should include flags or scoring advantages for public health alignment, unmet need, and societal value-criteria in which rare diseases are inherently strong. FP10 should also make space for bottom-up proposals within strategically defined destinations. This approach would help identify and address emerging knowledge gaps in rare diseases-particularly in white spots where scientific inquiry is urgently needed but data are sparse or fragmented.

Flexible and Fit-for-Purpose Rules

One-size-fits-all funding and reporting rules have repeatedly undermined the potential of partnerships and infrastructures. The Basic Act-referring to the legal regulation that establishes the structure and rules of an EU funding programme-often imposes a standardized governance model across all instruments within a programme. While intended to streamline administration and promote consistency, this standardization has created burdens for partnerships and infrastructures that operate in diverse and complex environments. For example, instruments that require co-investment from industry or involve multi-country clinical networks may need more tailored governance frameworks to function effectively. Applying uniform administrative rules to such entities can result in misalignment, inefficiencies, or even deter participation. Therefore, the Basic Act should allow for differentiated implementation pathways that reflect the specific operational realities of different types of initiatives. Rules must allow adaptation for sector-specific realities-such as using unit costs for SMEs, allowing valorization of prior assets, or adjusting governance based on partnership complexity. A harmonized system can exist, but flexibility-not uniformity-should be the guiding principle.

Sustained infrastructure support

Europe’s competitive edge depends on stable, high-performing research infrastructures that enable cross-border collaboration, standardized methodologies, and equitable access to research capacity. In the field of rare diseases, research infrastructures such as the European Reference Networks (ERNs), EATRIS (translational research), ECRIN (clinical trial coordination), and BBMRI (biobanking and biomolecular resources) are foundational to delivering high-quality, interoperable, and inclusive science. These platforms support data harmonisation, patient recruitment, trial coordination, biobanking (with access to samples and data), and translational research at scale; especially vital for rare diseases, enabling discoveries from basic science to be efficiently tested and refined in clinical settings. For diseases affecting small and dispersed populations, these infrastructures offer the coordinated capabilities necessary to accelerate the movement of scientific insights into practical therapies and interventions. Despite their systemic value, these infrastructures remain financially precarious, often relying on fragmented, short-term project funding without a sustainable baseline of operational support. This undercuts their ability to evolve, innovate, and plan strategically.

The MFF must guarantee predictable, multiannual support mechanisms that acknowledge the structural role these entities play. These could include direct core operational funding, mandatory co-funding obligations for projects that utilise ERICs and similar infrastructures, or earmarked operational grants that extend beyond the project-based model. Ensuring that these infrastructures are sustained is not only essential for rare diseases-it is a cornerstone of a competitive, resilient, and integrated European Research Area.

These infrastructures must be recognised not merely as tools, but as critical enablers of Europe's research ecosystem. FP10 should ensure sustained core funding and promote their integration across programmes-linking ERC, Pillar II, and deployment instruments to shared infrastructure investments.

Open and Globally Attractive

Rare diseases do not respect borders. The EU must remain open to international collaboration, particularly with countries like the UK and Switzerland, which are critical contributors to rare disease research. Competitiveness should not translate into isolation. A closed approach would not only harm scientific excellence but also compromise the ability to recruit patients and clinicians into the small-scale, multi-national studies that are common in rare disease R&D.

Risks of an overcentralized approach

Reduced focus on collaboration

Pillar II of Horizon Europe has historically played a vital role in supporting large-scale, cross-border collaborative projects. These projects bring together academia, industry, SMEs, and public authorities to tackle systemic challenges, including those in rare disease research. A shift in budgetary or strategic emphasis away from Pillar II toward ERC and EIC instruments risks marginalizing collaborative innovation. The ERC and EIC, while essential, primarily fund individual researchers or scale-up ventures. This could result in underfunding for partnerships that address unmet public health needs, including multi-sectoral coordination necessary for rare diseases.

Increased bureaucracy

If the future Competitiveness Fund is governed by a unified corporate rulebook, there is a significant risk that administrative requirements will be aligned to the most complex or risk-averse scenarios. Such harmonization could eliminate flexibilities needed by specific sectors, like clinical research involving vulnerable patient groups. The current Horizon governance already imposes substantial reporting burdens, and further consolidation without tiered or tailored rules would likely stifle participation from smaller actors, including SMEs, clinical networks, and patient organizations.

Understaffing and risk of underperformance

Lessons from the European Innovation Council (EIC) indicate that large, high-ambition programmes require proportionate administrative capacity. The EIC’s project officers have often been overloaded, limiting their ability to engage meaningfully with applicants and monitor project outcomes. If a consolidated MFF instrument adopts a similarly lean staffing model, it may lack the human resources necessary to deliver on the ambitions of complex, multi-stage funding schemes, particularly in areas like health and rare diseases, where continuity and specialized expertise are critical.

Political and geopolitical fragility

Incorporating politically sensitive priorities such as defense into a unified funding framework could alienate certain EU Member States and exclude key associated countries like Switzerland and the UK. Rare disease research thrives on global networks and cross-border patient cohorts. If participation in the programme becomes contingent on agreement with politically contentious pillars, the EU risks fracturing the collaborative base needed for research excellence and undermining trust among international partners.

Recommendations for FP10

1. Ensure that FP10, whether housed within the broader Competitiveness Fund or maintained as a separate programme, has a clearly defined scope and dedicated budgetary lines. This ringfencing is critical to preserve its mission-oriented character and to prevent research areas with limited commercial value, such as rare diseases, from being overshadowed by industrially strategic sectors.
2. Maintain and strengthen support for cross-border collaborative research, which remains essential for tackling rare diseases. These conditions often affect very small patient populations, requiring transnational consortia to achieve critical mass for studies and trials. FP10 should facilitate multi-country consortia with simplified administrative processes and support for trial infrastructure across borders.
3. Keep fundamental research within the scope of FP10 to avoid tilting too heavily toward applied, near-market research at the expense of basic science, which risks eroding Europe’s long-term knowledge base.
4. Ensure the sustained funding of key research infrastructures, such as the European Research Infrastructure Consortia (ERICs) and European References Networks, which are vital to the rare disease ecosystem. These infrastructures provide the backbone for data collection and sharing, biobanking, research capacities and clinical trial execution. They must be supported through core operational funding, rather than left to rely solely on short-term project grants. Long-term, predictable investment is essential to their continued impact.
5. Develop and expand tools to support the implementation and deployment of research findings. This includes mechanisms for developing and disseminating trial protocols, pathways for integrating innovations into national health systems, and funding for regulatory science initiatives that address the specific barriers to rare disease product development. FP10 should explicitly include calls or instruments that help bridge the gap between discovery and uptake, ensuring research translates into real-world benefit.
6. Support foundational work and translational readiness in mission-driven areas like rare diseases, FP10 should introduce tailored instruments-such as 'Research Actions' - that sit between traditional Research and Innovation actions and Innovation Actions. These would enable researchers to pursue mid-stage work, including validation and early clinical development, without needing to jump prematurely to implementation metrics.

Rare Diseases as a strategic investment case

Rare diseases are a proving ground for systemic innovation. They expose structural barriers in research funding, health system readiness, and regulatory processes-yet also create opportunities for transformational progress when addressed effectively. Rare diseases exemplify the very challenges the European research and health innovation system must address: fragmented funding streams, limited commercial returns, complex regulatory pathways, and inequitable patient access to innovation. Yet they also present unmatched opportunities for scientific discovery and system-wide learning. Research in rare diseases often leads to the identification of novel biological pathways, genetic markers, and therapeutic mechanisms that benefit not only those with rare conditions but also broader patient populations. Many breakthroughs in areas such as gene therapy, molecular diagnostics, and precision medicine have originated in rare disease research before being applied more widely.

Strategically, rare diseases represent an ideal testbed for coordinated, lifecycle-based investment approaches-from basic research through to clinical translation, regulatory innovation, and health system adoption. A policy and funding environment that enables such coordination will not only advance rare disease solutions but also reinforce Europe’s competitiveness in health innovation overall. This requires streamlined data sharing, adaptive regulation, and long-term, stable investment pathways tailored to small, high-risk, high-need domains like rare diseases. Because of their clinical and societal complexity, rare diseases demand interdisciplinary approaches that span biology, medicine, ethics, data science, and social research. FP10 should explicitly support calls that require integration across these domains, including the co-design of projects with patients and health system actors.

Investing in rare diseases supports:

• The development of interoperable, transnational digital tools, including genomic databases, patient registries, and digital clinical trial platforms. These tools are essential for cross-border studies, especially where national cohorts are too small to be viable alone.
• Public-private partnerships that accelerate innovation, facilitate platform-based approaches, and reduce duplication are a cornerstone of progress in rare diseases. These partnerships bring together industry, academia, health systems, and patient communities to tackle complex problems that no single actor can solve alone. Their collaborative structure allows for more coordinated use of resources, better alignment of goals, and shared risk in pursuing high-risk, high-impact science.
• Breakthroughs in gene and cell therapies, many of which originate in rare disease research, have served as technological springboards for broader applications in common conditions. Investing in rare diseases enables early testing and refinement of advanced therapeutic modalities in settings where innovation is most needed and can be most transformative. These innovations frequently generate spillover benefits across the wider biomedical ecosystem-improving tools, methodologies, and regulatory practices that benefit public health more broadly.

Rare disease innovation is a litmus test of Europe’s ability to deliver high-impact, inclusive, and forward-looking health policies. The MFF must reflect that by embedding rare diseases as a strategic, cross-cutting priority across funding, regulatory, and implementation dimensions.

Conclusion

The future MFF must balance coherence with strategic visibility. While integration has benefits, it must not come at the cost of flexibility, clarity, and sustained investment.

Rare disease innovation can help the EU lead globally in health, science, and technology. But this requires tools that are inclusive, nimble, and impact-oriented. The next MFF must deliver that.