Unlike what one might expect, a rare disease isn’t just a concern for a handful that can be easily overlooked. In fact, in Europe alone, approximately 36 million people are suffering from rare diseases, which is approximately equivalent to half the population of France11. https://www.orpha.net/consor/cgi-bin/index.php?lng=EN. But what defines a rare disease? Interestingly, there’s no universal definition; rather, it’s based solely on the concept of prevalence thresholds. In 1999, the EU regulation on orphan medicinal products defined a rare disease as one that affects no more than 1 out of 2000 persons22. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2000:018:0001:0005:EN:PDF. To date, over 7000 rare diseases have been described, and scientists continue to constantly uncover new ones33. https://www.certara.com/app/uploads/2022/04/WP_Rare-Disease_Final.pdf. The majority of rare diseases have a genetic origin (nearly 80%), but there are also forms of rare autoimmune diseases and rare forms of cancer 41. https://www.orpha.net/consor/cgi-bin/index.php?lng=EN53. https://www.certara.com/app/uploads/2022/04/WP_Rare-Disease_Final.pdf. There is no cure for most rare diseases, and the field suffers from gaps in medical and scientific understanding. Nevertheless, impressive progress has already been made in recent years and appropriate treatments and medical care have proven to enhance the quality of life and extend the lifespan of those affected. Yet, it’s evident that further research and development efforts must be undertaken by scientists to truly enhance the lives of those facing a rare disease.
Alcimed is constantly monitoring the latest developments in therapeutic treatments for rare diseases. In this article, we present three challenges and three opportunities for the current research and development of rare diseases.
Finding a sufficient number of patients who meet the inclusion and exclusion criteria for a specific trial can be challenging due to the low prevalence of rare diseases. Furthermore, patient populations often exhibit significant heterogeneity in terms of disease subtype, symptoms, stages, and prior treatment exposure. Therefore, many rare disease clinical trials are multicenter, often multinational, to ensure sufficient patient recruitment. This can pose challenges to protocol harmonization, ethical review, financing, organization of clinical services, standards of care, and cultural diversity.
While randomized clinical trials are considered as the gold standard, it’s a good idea to thoughtfully explore different trial approaches, such as multi-arm trials involving testing multiple interventions simultaneously within the same trial and open-label trials where treatment assignments are disclosed to both participants and researchers. These alternative approaches can help streamline the research process and reduce the number of required patients.
Rare diseases that are not well-understood and lack comprehensive knowledge about their underlying causes, mechanisms, and interactions often pose significant challenges to scientists. This limited understanding makes it difficult to formulate effective research strategies and develop targeted treatments. An understanding of the disease’s natural history, as well as the standard progression without intervention or with standard care is essential to define relevant endpoints of a clinical trial. Moreover, many rare diseases are inherently complex, involving multiple factors, pathways, and interactions within the human body.
A solution involves supporting interdisciplinary networks to merge expertise from genetics, biology, and technology, and encouraging data sharing through centralized databases, to ultimately enhance our understanding of rare diseases.
Developing a treatment for a rare medical condition presents a financial challenge for pharmaceutical companies. The substantial expenses associated with drug development, coupled with the limited patient population and small market size, discourage pharmaceutical companies from allocating resources toward the research of rare diseases. This financial choice leads to a significant number of patients being left without access to interventions that could lighten their symptoms and enhance their overall well-being.
Incentive programs, such as government tax breaks, grants and funding, or accelerated regulatory processes, can be one solution to encourage investments in rare disease therapies.
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Despite these challenges, there are promising opportunities that could pave the way for the development of new therapies for rare diseases. These opportunities hold the potential to transform the landscape of rare disease research and improve the lives of individuals affected by these conditions. Let’s explore three such opportunities:
Rare disease clinical trials are undeniably complex and challenging, as mentioned above. However, recently developed technological solutions designed to support hybrid and decentralized trials, along with novel clinical trial designs such as adaptive trials or platform trials, present exciting opportunities, as these solutions have successfully overcome certain barriers to patient participation. Adaptive trials involve making real-time adjustments to the trial design based on accumulating data, allowing for flexibility in treatment arms, sample sizes, or other aspects. Platform trials, a type of adaptive trial, allow for the ongoing evaluation of multiple treatments against a single, constant control group within a single overarching protocol. Furthermore, regulatory agencies have the opportunity to implement mechanisms such as fast-track designation, orphan drug status, or priority review to streamline the approval process for rare disease clinical trials. This enables researchers to quickly test new interventions and therapies, potentially accelerating the testing and approval of potential treatments.
International research collaborations focused on rare diseases bring together scientists, doctors, big pharmas, small businesses, and patient groups, creating a powerful synergy that surpasses individual efforts. These initiatives cover various medical fields like neurology, immunology, metabolism, and rare cancers. This expanded knowledge could lead to breakthroughs in understanding human health, paving the way for innovative solutions that go beyond rare diseases, benefiting overall well-being. These collaborations also drive advancements in diagnostics, treatments, and best practices for use in hospitals and healthcare systems.
Developing therapies tailored to the unique profile of an individual with a rare disease can pave the way for more targeted and effective interventions, ultimately improving outcomes and quality of life. This approach enables researchers to search for the genetic and molecular mechanisms underlying these conditions, leading to a deeper understanding of disease progression. Additionally, it opens doors for innovative technologies like gene editing and precision medicine, driving advancements in the field. By investigating rare diseases, we not only bring hope to those affected, but also advance medical science, pushing the development of personalized healthcare.
The substantial number of individuals affected by rare diseases underscores the urgent need for innovative therapeutics. By raising awareness, fostering interdisciplinary collaboration, exploring alternative trial approaches, and bridging gaps between stakeholders, Alcimed is dedicated to making a meaningful impact in the field of rare diseases. Our healthcare team is continuously monitoring the dynamic landscape of rare diseases and stands ready to support you in assessing challenges and opportunities for research and development within this field. Should you want to discuss this topic or any project related to rare diseases, don’t hesitate to contact our team !
About the author:
Haiko, Consultant in Alcimed’s Healthcare team in Germany
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