he knowledge and infrastructure required to unlock rare disease “white spots,” diseases where there is currently no science or translational capability, call for a different strategic paradigm. The mission of the Rare Disease Moonshot is rooted in boosting public-private collaborations.

Key Takeaways

• There is no treatment for 95 percent of rare diseases, and in many cases, no science to translate into solutions for patients.
• The Rare Disease Moonshot will enhance the translational research ecosystem, optimize clinical trials and regulatory pathways, and boost infrastructures.
• New recommendations on “research needs” in clinical trials, diagnostics, and translational research have been published.
• Public-private partners support calls for a European Action Plan on Rare Diseases.

Conducting clinical trials when patient populations are small, expertise is dispersed, and regulatory pathways are complex can be immensely difficult. When new solutions are developed, working with payers to ensure access to innovative diagnostics and medicines can bring additional challenges arising from limited availability of patient insights or payer knowledge of rare diseases. As a result, these headwinds have given rise to a lack of science and significant unmet need.

Today, despite progress in recent years, the reality is stark, with an estimated 95 percent of the 7,000 identified rare diseases still lacking a cure or treatment. In fact, in the worst cases, for many diseases there is no “science” at all.

This demands a radical new approach. We cannot continue on the current path and expect different results. Today’s medicines development landscape was designed to solve medical problems where we have more patients, more knowledge, and more expertise. It is ill-suited to the challenge of rare diseases.

Part of the problem is that we are in the habit of moving in straight lines with too little involvement of stakeholders from all the relevant sectors. Instead of following familiar patterns, all partners must collaboratively engage with other stakeholders including in public-private partnerships, as the technology moves along the value chain towards access. We should be moving in parallel rather than in series, remaining open to innovative ways of working together.

The Rare Disease Moonshot is a multistakeholder commitment which aims to take public-private partnerships to the next level. It envisions deep and diverse collaboration on the scale witnessed during the COVID-19 pandemic. Together, we can generate new data, develop and/or utilize existing infrastructures, and reimagine the translational research ecosystem.

While the challenge ahead is significant, the past shows that partnerships and smart policy can deliver progress. More than 200 therapies for rare diseases have become available in the past two decades, with new diagnostic tools for several illnesses. While this is just the tip of the iceberg, it shows the meaningful impact that can be achieved through public awareness and industry commitment in tandem with dedicated EU rules on orphan medicines, methodological qualification of new study designs, and adapted regulatory pathways.

In addition, we have seen improvements in data infrastructure, research consortia, and multistakeholder approaches to HTA. The 24 European Reference Networks (ERNs), which bring healthcare specialists and rare diseases investigators together, provide a sound structural foundation for taking the next steps forward.

Most recently, the proposed EU Pharmaceutical Regulation (2023/0131) foresees opportunities for not-for-profit organizations, including patient advocacy groups, to make submissions to the EMA or a Member State competent authority. This would broaden the level of clinical or nonclinical evidence that regulators can consider when assessing a new therapeutic indication that addresses an unmet medical need.

Addressing unmet needs and filling gaps in science requires not only a supportive legislative and policy environment. Progress is driven by stakeholders. Public and private partners in this field are taking proactive steps to effect lasting change through joint initiatives.

Rare Disease Moonshot: Stronger Together

Tackling the “White Spots”

First, it is essential to define the problem. A 2021 report commissioned by EFPIA highlighted the challenge of addressing “white spots” in rare and pediatric-onset diseases. White spots are areas where there is currently no ongoing research and, as a result, no hope on the horizon for patients and their families.

The report highlights three challenges: The dearth of scientific knowledge due to the complexity of designing and conducting clinical trials; the need for a world-class regulatory system in Europe to facilitate the translation of knowledge into new solutions; and the fact that payers do not always recognize and reward the full value of rare disease diagnostics and therapies.

To begin addressing these gaps, the RD Moonshot has published three sets of Research Needs Recommendations. The first focuses on clinical trials. It calls for continued multilateral collaboration to optimize how trials are designed and conducted through enhanced collaboration and advances in regulatory science. This is in line with the European Medicines Agency’s (EMA) ongoing work in this area. The Recommendations cite the IHI, on establishing novel approaches to improve clinical trials for rare and ultrarare diseases and future calls in rare diseases, as “an opportunity to generate high quality science, by having a variety of expertise and tools synergised to address a complex area relevant to public health needs.” This program also included a pilot on repurposing medicines.

A separate paper provides Recommendations for Diagnostic Research in Rare Diseases. This crucial piece of the rare diseases puzzle has the potential to spare millions of families the frustration and trauma associated with the “diagnostic odyssey”: the long, often fruitless quest for a diagnosis. Improving how diseases are defined, and improving diagnostic speed and accuracy, as well as access to technology and automation, can deliver significant benefits for underserved populations. The paper sets out a series of areas where public-private partnerships can add value, including molecular, clinical, and digital biomarkers, epidemiology, and technology.

A third publication spotlights public-private collaborations in the field of translational medicine. It sets out a series of actions to address bottlenecks in the European R&D ecosystem. These include upskilling major stakeholders in the research continuum, including research funders, clinicians/researchers, technology transfer offices, and corporate officers. This will reduce wasteful repetition of experiments by supporting reproducible and patient-oriented science in rare disease research.

In addition, it calls for the use of state-of-the-art validation methods; meaningful patient engagement across the technology lifecycle; increased knowledge of regulatory science among academia/clinicians; derisking of research programs through better understanding of the full development path; upskilling nonprofit research funders; and the implementation of Responsible Research & Innovation (RRI) policies.

Looking Ahead

We also see a role for advocacy in the current policy debate. RD Moonshot partners support the call by EURORDIS for a European Action Plan on Rare Diseases to ensure a comprehensive and joined-up approach at the EU level. The Action Plan must focus on the whole patient journey, from research needs to access, identifying the right instrument and strategy for each step of the process.

Together, we can improve the lives of people with a rare disease in Europe and beyond; make the European research ecosystem more attractive and efficient; and address the “white spots” with increased speed and vigor. These are challenges that can only be solved by harnessing the collective intelligence of everyone engaged in this field. We urge readers to embrace and share the publications and tools developed by the RD Moonshot, and to engage in collaborations and partnerships to move its work forward.