The Path to Innovation in Rare Diseases comes through Partnerships – A reflection on the EU Pharmaceutical Package

In this guest blog, Toon Digneffe, EUCOPE Board Member & Head of Public Affairs and Partnerships – Europe & Canada at Takeda, reflects on the EU Pharmaceutical Package and highlights the importance of multi-stakeholder partnerships to build a sustainable rare disease ecosystem that benefits patients. 

On 26 April, the European Commission published its long awaited proposal revising the foundational pharmaceutical legislation, including the Orphan Medicinal Products (OMP) Regulation. The OMP Regulation proved to be a success legislative initiative, paving the way for over 230 therapies to be developed and spurring a flurry of novel therapies for people living with rare diseases, and beyond.[1]

This revision is a key opportunity to build on the successes of the OMP Regulation. The Commission’s efforts to introduce additional regulatory flexibility while maintaining high safety standards, streamline EMA processes to accelerate drug approvals, support early dialogue efforts and increasingly recognize the role of Real-World Evidence are all essential and welcome proposals that will bring important benefits.

Europe needs to build towards a mutually reinforcing rare disease ecosystem supported by a legislative framework that is realistic in what it can achieve. A lot can be achieved outside the legislative framework, requiring multi-stakeholder collaboration across the medicine lifecycle and patient journey. Fundamentally, partnerships are a key component to address the 95% of rare diseases with no authorized treatments.[2]

The revised legislation will have implications beyond its core scope due to the interconnectivity of the healthcare system. Legislators must be aware of the potential unintended consequences, and avoid trying to address all of the challenges that exist in the rare disease space through one piece of legislation, or using inappropriate levers to drive change where other tools might exist. This new Regulation will set the tone for research and development for at least the next 20 – 30 years, [3] so we should build a system that reinforces itself, supports partnerships and most importantly, benefits patients.

Orphan Incentive Framework

A key change to the orphan system is a rethink of the orphan incentive market exclusivity – the incentives awarded to a developer that markets a therapy for an orphan indication. Moving away from a one-size fits all approach, where all orphan therapies receive 10 years of orphan exclusivity, the proposal introduces a ‘modulated’, or dynamic, incentive system.[4] EUCOPE recognizes the potential of a modulated incentive framework, having contributed to developing an alternative approach. In a multi-stakeholder setting, with experts and representatives from the patient, industry, and academic community, among others, the European Expert Group on Orphan Drug Incentives (OD Expert Group) developed a modulated incentive framework.[5] This approach aims to address the fundamental challenges contributing to the fact that 95% of rare diseases have no authorized treatments.[6]

EUCOPE, and many in the industry at large, are deeply concerned by the European Commission’s approach to modulate the orphan incentives as we believe it does not address the core challenges that would encourage the development of therapies for the 95% of rare diseases with no authorized treatment. To drive innovation, we need a stable and predictable system to allow for long-term investments.[7] Linking incentives to concepts such as high unmet medical need (HUMN) with its restrictive interpretation risks stifling innovation, overlooking patient populations, and limits the longevity of the legislation.

Instead, the modulation should reflect the probability of success when developing a new therapy and encourage innovation. This should include facilitating and promoting more collaboration between public and private stakeholders, which will be fundamental in encouraging basic and translational research, a key barrier when developing therapies for rare diseases.

The introduction of a single marketing authorization for each active substance, effectively a ‘Global Orphan Marketing Authorization (GOMA)’ which only provides one year of additional exclusivity for moving into a new indication must be carefully considered.[8] This would act in contradiction of the Commission’s aim of facilitating the development of therapies for patients with no authorized treatments. Developers should be encouraged to find additional applications for existing compounds, especially if this opens the door for treatments for those patients with no other options.

In an effort to drive access, the Commission has put forward its ‘launch conditionality’[9], providing developers with additional orphan exclusivity for launching a therapy available in all 27 Member States in two to three  years.[10] A laudable ambition, it is regrettably unfeasible, especially for small and mid-sized companies, as well as many orphan and ATMP developers. This has been strongly emphasized by EUCOPE over the past two years. First, developers are not the only stakeholders involved in pricing and reimbursement discussions, and national policies will inform access decisions. For certain therapies such as OMPs and ATMPs, the necessary infrastructure, patient population or expertise might not exist in all Member States. Therefore, EUCOPE has put forward proposals such as improvements to the cross-border framework[11] and other innovative pathways in order for patients to get early access to these treatments.

Addressing the High Unmet Medical Needs

While the intention behind the Commission’s efforts to encourage more innovation in the area of unmet needs is welcomed, there is a concern that the approach, labelling and rewarding orphan therapies for meeting a restrictive concept such as ‘high unmet medical needs (HUMN)’ could have unintended consequences. HUMN change over time as a disease progresses, new innovations emerge, and can differ between individuals as rare diseases are heterogeneous. Not all people living with a rare disease will respond to the same or first treatment that is developed, we need to ensure that all patients can benefit from innovation.

This HUMN classification will create an artificial ranking of patients and does not address the fundamental challenge in developing therapies for rare diseases, which is often the lack of basic science. To drive innovation for those 95% of rare diseases with no authorized treatment, a more holistic approach needs to be taken, looking across the entire lifecycle. This was the first task of the OD Expert Group which looked at the barriers throughout the process, outlining 14 concrete recommendations. [12]

The value of partnerships in addressing the challenges in the rare disease space

Developing an OMP is a complex and time-consuming exercise. It cannot be done alone, and in a similar fashion, addressing the challenges in driving innovation and access to OMPs cannot be done by one stakeholder or one legislative initiative. At its core, the discussion around OMPs and rare diseases must take a partnership approach. We must look at the entire ecosystem, and by working together we can address the root causes of the challenges that exist.

Initiatives such as the OD Expert Group, Together4RareDiseases, TRANSFORM,  RWE4Decisions, and the future Rare Disease Partnership are all examples of how we can collaborate at different steps of the process to build and improve rare disease ecosystem in Europe. The EU needs an EU Action Plan on Rare Diseases to ensure a holistic vision, only then can we effectively support people living with rare diseases and build a true innovation ecosystem that runs from discovery to delivery.

EUCOPE, and its members, including Takeda, are committed to continuing to work in a constructive way with the rare disease community and all stakeholders involved during the upcoming review of the EU Pharma Package. This review must be seen as one step in a wider exercise and in that way, address the challenges it can, without trying to solve all the issues that exist to avoid potential unintended consequences and risk bringing about new challenges. We should build on the success we have had with the current rare disease framework and not leave it to the wayside.


[2] European Commission, Directorate-General for Research and Innovation (2022). Collaboration: a key to unlock the challenges of rare diseases research, Publications Office of the European Union.

[3] Setting the scene for the future of people living with rare diseases (2023). The Parliament.

[4] Aartsma-Rus, A., Dooms, M., & Le Cam, Y. (2021). Orphan Medicine incentives: How to address the unmet needs of rare disease patients by optimizing the European Orphan Medicinal Product Landscape Guiding Principles and policy proposals by the European expert group for Orphan Drug Incentives (OD expert group). Frontiers in Pharmacology, 12.

[5] European Expert Group on Orphan Drug Incentives (2022). Modulating incentives for OMP development.

[6] European Expert Group on Orphan Drug Incentives (2022). Modulating incentives for OMP development.

[7] Horgan, D., Moss, B., Boccia, S., Genuardi, M., Gajewski, M., Capurso, G., Fenaux, P., Gulbis, B., Pellegrini, M., Mañú Pereira, M. D. M., Gutiérrez Valle, V., Gutiérrez Ibarluzea, I., Kent, A., Cattaneo, I., Jagielska, B., Belina, I., Tumiene, B., Ward, A., & Papaluca, M. (2020). Time for Change? The Why, What and How of Promoting innovation to tackle rare disease - Time to Update the EU's Orphan Regulation? And if so, What Should be Changed?. Biomedicine hub, 5(2), 1–11.

[8] European Commission, Directorate-General for Health and Food Safety (2023). Proposal for a Regulation of the European Parliament and of the Council laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006.

[9] EUCOPE (2022). Launch Conditionality: What’s at stake?

[10] European Commission, Directorate-General for Health and Food Safety (2023). Proposal for a Directive of the European Parliament and of the Council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC.

[11] EUCOPE (2021) Cross-border healthcare for rare diseases patients: What can be done?

[12] European Orphan Group on Orphan drug incentives (2021). How to address the unmet needs of rare

disease patients by transforming the European OMP landscape.

May 3, 2023

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