Better together –
accelerating innovation and access to rare disease treatments

By Derek Ansel

Rare disease researchers have always contended with significant barriers posed by small patient populations, fragmented data, challenging endpoints and limited opportunities to gain efficiencies. But now, more than ever, there is a growing acknowledgment that solving rare disease challenges to expedite patients’ access to life-changing therapies requires regulatory, community and global stakeholder cooperation.

Although individually rare, rare diseases are not rare when viewed collectively. Approximately 300 million people globally live with a rare disease and many of them share common needs and experiences.

That is why global cooperation is so crucial to rare disease research. National, international and community partnerships and harmonised clinical trial strategies present opportunities to accelerate innovation and access to treatments. There are many benefits to pooling knowledge and resources.

This recognition has led to the recent creation of collaborative efforts such as:

• The European Rare Disease Research Alliance (ERDERA)
• The EU-X-CT Initiative
• The US Food & Drug Administration (FDA) Rare Disease Innovation Hub
• The FDA Support for clinical Trials Advancing Rare disease Therapeutics (START) programme
• Caregiver-led groups like the Inchstone Project.

The European Rare Disease Research Alliance (ERDERA) is now carrying forward the work formerly done by the European Joint Programme on Rare Diseases (EJP RD) and other projects. ERDERA aims to help academic key opinion leaders (KOLs) drive science and innovation in their respective rare diseases through funding, research networks, data services and resource consolidation.

Its mission is threefold:

• Unify rare disease resources, knowledge and expertise under one roof
• Empower patients to be ‘findable’ and enrolled in appropriate clinical trials
• Foster collaboration and align strategies to make Europe a world leader in rare disease research.

The EU-X-CT Initiative is a consortium that launched in 2022 with the ultimate goal of enabling easier cross-border clinical trial enrolment in the European Union (EU) (in other words, helping patients from one EU country enrol in studies in another EU country). It comprises volunteers representing industry, patients, advocacy groups, academic institutions and others from 32 European countries and the United States.

Currently, a lack of EU-wide guidance on cross-border study enrolment poses substantial challenges. For example, if a study opens in France but a patient lives in Poland, how would that patient be identified as a potential study candidate? What visa requirements, insurance issues, financial requirements, ethics committee approvals and language barriers must be overcome to enable the patient to cross borders to participate in the study?

EU-X-CT is trying to address those issues:

• By building a repository of information detailing each European country’s cross-border clinical trial requirements – including operational, logistical, legal, ethical, financial and other barriers
• By providing recommendations to navigate those barriers. 

The FDA’s Rare Disease Innovation Hub is newly created to serve as a single connection point for the rare disease community – including patients, patient advocates, researchers and product developers. It’s designed to enhance the collaboration between the FDA’s Center for Drug Evaluation and Research (CDER) and its Center for Biologics Evaluation and Research (CBER) – the two FDA agencies most often involved in approving rare disease products in the US. It aims to help the rare disease community navigate common scientific, clinical and policy challenges.

The three primary roles of the Innovation Hub are:

• To give the rare disease community at large one point of contact for help navigating FDA intersections, including medical devices, diagnostic tests and combination products
• To strengthen CDER, CBER and other cross-agency collaborations to share knowledge and encourage consistency
• To advance science by exploring the use of novel endpoints, biomarkers, innovative trial design, real-world evidence and statistical methods in rare disease research.

The FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) programme encourages sponsors to collaborate early and often with regulators. Sponsors leverage START to obtain frequent advice from the FDA about their study designs, patient cohorts, endpoint selection, product characterisation, translational science questions and more.

Currently a pilot programme, START is accelerating the development of selected cell and gene therapies for rare diseases with significant unmet needs and accelerating the development of selected therapies for rare neurodegenerative conditions with significant unmet needs.

These types of therapies are both complex and costly. Meaningful endpoints are difficult to select. Consequently, through more frequent touchpoints, START strives to help sponsors reduce guesswork, set studies up for success and hasten drug approvals in the long run.

The Inchstone Project is an excellent example of a caregiver-led collaboration. This alliance of scientists, researchers, patients and advocates is devoted to improving the endpoints against which treatments for rare forms of epilepsy are gauged.

There are many different types of epilepsy and many different advocacy groups specific to each type. The Inchstone Project, however, serves as an umbrella organisation for all rare forms of epilepsy. It supports the development of novel endpoints that better capture the incremental outcome improvements important to patients, parents and caregivers.

For example, the FDA and other regulatory agencies have historically looked for evidence of fewer seizures when reviewing potential epilepsy treatments. However, seizures represent only one of many challenges for those with rare epilepsies. Some conditions may also affect an individual’s ability to speak, eat or walk. Thus, the parents and caregivers of non-verbal children may be as interested in treatments that can help their children express themselves as they are in treatments to reduce seizures.

Rare disease research is unique. Many ‘unknowns’ are involved and it can even be difficult to determine appropriate endpoints for clinical trials. Nevertheless, the small numbers of people affected by a single rare disease add up to a considerable number of people living with similar shared experiences.

Therefore, although collaboration strengthens every type of research, one could argue that it’s especially crucial for rare disease communities that can’t afford the delays and missed opportunities caused by siloed efforts and inefficiencies. Pooling resources, expertise and data allows researchers to bring innovative approaches to the forefront and ensure that the needs of patients, families and caregivers always remain the central focus.

Tremendous power is unlocked when we bring diverse perspectives to a shared vision.  Working together collectively on a global scale gives rare disease communities the best hope for accelerating meaningful treatments and transforming lives.