Where are we in understanding and tackling rare diseases?

The talks, organised by Pharmadanmark and attended by a sell-out audience in the room and online, brought together clinicians, researchers, regulators and industry representatives to explore how rare disease research and drug development is driving innovation across the life sciences.

From genomics and data sharing to clinical trial design and regulatory decision making, the discussions made it clear that rare diseases deserve our attention, now and for the future of healthcare.

Individually uncommon, collectively significant

Rare diseases, by definition, affect fewer than 1 in 2000 people. However, a clear theme throughout the evening was the paradox at the heart of the topic: They collectively affect hundreds of millions of people worldwide, with estimates exceeding 350-400 million patients in total.

Rare diseases are not a niche concern for a few specialists, but a systemic challenge that cuts across clinical practice, drug development and policy. It is increasingly recognised that insights from rare diseases are transferable to more common conditions, particularly as medicine becomes more stratified and genetically informed.

Diagnosis as the central bottleneck

A dominant theme was the diagnostic challenge. Heidi L. Rehm – Co-Director of Medical and Population Genetics at the Broad Institute in Boston – emphasised that diagnosis remains the starting point for innovation in genomic medicine, yet around 50% of rare disease causes are still unknown.

Elsebet Østergaard – Consultant and Professor of Clinical Genetics at Rigshospitalet – expanded on this from a clinical perspective, describing the diagnostic odyssey. Patients typically wait four to seven years for a diagnosis and may encounter around eight healthcare professionals along the way. And even with a diagnosis, this doesn’t always translate into effective insights for prognosis or treatment.

Technological advances have improved capabilities significantly. Our rapid progress in genome sequencing has increased diagnostic reach, but gaps remain; tens of thousands of genetic variants are of unknown or unexplained severity.

A key message emerging from the discussions was that the bottleneck is no longer only technical. Awareness plays an equally important role. Improving recognition among general practitioners and specialists, and encouraging healthcare practitioners to look beyond narrow areas of expertise, will be essential steps towards shortening the diagnostic journey. This, in turn, will give patients and their families early access to support like genetic counselling and perhaps timely access to clinical trials.

Data sharing is essential, and we’re not on the mark yet

If diagnosis is the bottleneck, data is the infrastructure underpinning progress. Heidi highlighted the importance of global data sharing for understanding rare disease origins. Platforms such as gnomAD and ClinVar, along with emerging variant matching tools and federated databases, are enabling researchers to connect previously isolated data points.

However, the discussions also made it clear that the current data landscape is incomplete. Baseline datasets remain skewed towards populations of European ancestry, limiting their applicability across diverse patient groups. Improving representation is not only a matter of equity, but also of scientific accuracy.

This is also important in the context of classification. With modern approaches to better understand the mechanisms of disease we are increasingly seeing sub-categorisation (so called salami-slicing) of diseases, which can push a subgroup of patients into the ‘rare’ box. It’s also relevant when we consider that some diseases can be rare in some geographical regions, but more common in others.

And what of the role of patients themselves? The rare disease community is highly engaged and motivated, with many patients willing to contribute data in the hope of achieving answers. This gives us both an opportunity and a responsibility to design systems that reduce barriers to participation and ensure that contributions translate into meaningful outcomes.

Rethinking drug development and trial design

Rare diseases challenge many of the assumptions that underpin traditional drug development. As Marie Louise Binderup from Lundbeck pointed out, unique patient populations and limited natural history data make it impossible to simply scale down standard clinical trial models to smaller cohort sizes.

Instead, more flexible and innovative designs are required. Seamless transitions between early phase trials and proof of concept studies, as well as the use of adaptive methodologies, are becoming increasingly important. Patient centricity is also critical, particularly when defining meaningful clinical endpoints. Understanding how disease impacts daily life can be as important as biological markers.

Thomas Kongstad Petersen from NMD Pharma reinforced this by highlighting the practical challenges of working without established standards. In some rare disease contexts, there are no accepted endpoints or baseline expectations, requiring developers to work closely with regulators to define appropriate measures.

These constraints are not unique to rare diseases. As more common conditions are subdivided into genetically defined subgroups, similar challenges are likely to become more widespread. Rare diseases therefore offer a preview of future development paradigms.

Regulation, uncertainty and ethical tension

The regulatory perspective, presented by Jannick Brennum – Vice Chair of the Danish Medicines Council (DMC) – brought into focus the dilemmas in decision making for rare diseases, calling his organisation the ‘Stormtroopers’ at the border of access to effective medicine.

“There is nothing we would like to do more than to provide access to efficacious treatments, which we must do within the framework of cost-effectiveness and long-term safety,” said Jannick.

Short follow-up periods and small datasets mean that long term benefits and risks often have to be extrapolated. This creates uncertainty in both clinical and economic evaluations. The so-called severity principle allows for greater tolerance of uncertainty in severe conditions, but this does not remove the underlying challenge.

A particularly thought-provoking aspect of the discussion was the ethical dimension. How should limited resources be allocated between rare disease patients and those with more common conditions?

While there is consensus that access should be equitable, practical decision making inevitably involves trade-offs. Efforts to improve coordination are ongoing and early engagement between developers and regulators is key to building of smoother pathways to regulatory approval.

So, what are the key takeaways for professionals across healthcare and life sciences?

Most critical focus area: Collaboration is no longer optional

One theme stood out as a unifying force: collaboration. Progress depends on coordinated efforts across sectors, including meaningful involvement of patients. And thankfully, stronger connections between academia, industry, clinicians and patient groups are already reshaping the landscape.

However, collaboration is still uneven. Access to resources and influence can vary, and patient advocacy is not equally developed across regions, especially in Denmark where the numbers of rare disease patients are so small.

At the same time, there are clear signs of convergence between rare and common disease research. Advances such as gene therapies, targeted treatments and data-driven diagnostics are beginning to cross traditional boundaries.

As Christina Therkildsen – Research Group Leader, Colorectal Cancer Research Unit, Copenhagen University Hospital Hvidovre – noted, “What starts as a rare disease insight can become broadly applicable in more common diseases once mechanisms are understood.”

Other insights for Life Science professionals

• Rare diseases are strategically important. They are not a niche area, but a driver of innovation that is reshaping broader Life Science practice.

• Diagnosis remains the critical bottleneck. Investment in awareness, systems and data integration is as important as technological advancement.

• Traditional development models are no longer sufficient. Flexible, patient centred trial designs are essential, particularly in small and heterogeneous populations.

Our shared responsibility

Perhaps the most resonant line from the event was the closing remark by Stine Hasling Mogensen – President of Pharmadanmark – which captured the collective responsibility of the field: “It’s not rare to have a rare disease, but many patients face a significant burden simply to obtain a diagnosis, so we all have work to do in order to support these patients.”

Many thanks to everyone for joining this event, and especially to the speakers for sharing their insights in the field of rare disease innovation and clinical practice.

The Life Science Talks play an important role in raising awareness of these important topics. By bringing together diverse perspectives and fostering open discussion, we can all have a more integrated understanding of these complex issues and an opportunity to contribute to improving outcomes for rare disease patients.