Contrary to common belief, rare diseases do not just affect a small fraction of the population.
Globally, there are currently 300 million individuals afflicted with rare diseases, and it is estimated that there are over 7,000 rare diseases, many of which are life-threatening.
On average, the cost burden per patient affected by a rare disease is estimated to be approximately 15 times greater than that of high-prevalence diseases, leading to considerable financial strain on the affected families and increased demand for healthcare system resources.
While rare diseases vary widely in their prevalence, symptoms, and severity, a significant portion remain undiagnosed and lack effective treatments.
Diagnosis of rare diseases is notoriously difficult, often taking years for patients to discover the underlying cause of their symptoms.
Newborn screening for rare diseases, which began to be implemented in Europe and the USA in the mid-20th century with the establishment of the first programmes targeting diseases such as phenylketonuria in the 1960s, is resulting in early diagnosis and consequent early treatment for a number of those diseases.
Importantly, while there are a number of approved medications that target the underlying cause or manage symptoms of rare diseases, others may only have supportive therapies to improve patients’ quality of life.
In recent years, advancements in biotechnology and precision medicine have led to breakthroughs in the development of targeted therapies, including gene and enzyme replacement therapies, offering hope to patients with previously untreatable conditions.
Some examples of innovative approaches that have shown efficacy in halting disease progression, and offering the potential for life-changing outcomes include, Onasemnogene abeparvovec for the treatment of spinal muscular atrophy, a disease causing muscle function loss in children, and Delandistrogene moxeparvovec for the treatment of Duchenne muscular dystrophy, a disease causing progressive muscle degeneration and weakness.
Ellie Phylactopoulos
However, high treatment costs, limited treatment options, diagnosis delays, barriers to specialised care, and insurance coverage issues, are significant barriers for patients and healthcare systems globally.
Thus, further research is needed for continued innovation and collaboration in the field of rare disease therapeutics.
Recognising the urgent need to address these unmet medical needs, regulatory agencies like the FDA and EMA established special pathways and programs to incentivise drug development for rare diseases.
Nevertheless, designing clinical trials for rare diseases with small patient populations globally presents challenges in recruitment, and endpoint selection.
Limited patient numbers prolong trial durations and increase costs, while disease variability complicates defining similar cohorts.
Additionally, insufficient understanding of disease progression impacts endpoint selection and regulatory requirements, demanding robust evidence of efficacy and safety.
When a potential treatment may not be a cure, it is more difficult for clinicians to define what success looks like for a clinical trial, for example how a drug may alleviate symptoms, delay disease progression, or provide the patient a better quality of life.
Overcoming these challenges necessitates innovative trial designs, international collaboration, and patient engagement to ensure successful therapy development.
From a commercial standpoint, the limited patient populations result in limited market sizes, from which pharmaceutical companies may struggle to recoup the high costs of research, development, manufacturing, and distribution associated with these treatments.
In addition, the complexity of diagnosis and disease management can result in delays in treatment initiation, further impacting commercial viability.
Collectively, to overcome these obstacles, companies often need to make additional investments to help identify potential patients as well as provide more extensive support to healthcare providers who may need assistance understanding diagnosis and considering treatment plans.
Moreover, pricing and reimbursement issues, including negotiating with healthcare payers for coverage and reimbursement rates, present significant hurdles.
While the lack of economies of scale in production and distribution can also contribute to higher costs per patient, the treatment may also act to lower costs more broadly, for example, by lowering the frequency of hospital visits for the patient on that new therapy.
Overall, these challenges necessitate innovative business models, strategic partnerships, and advocacy efforts to ensure the sustainability and accessibility of treatments for rare diseases and better understand the impact on the patient, their families, and the overall healthcare system.
In summary, advances in medical research, technology, and collaboration have led to significant progress in addressing the underlying causes of rare diseases and improving patient outcomes.
Increased awareness and advocacy efforts have raised the profile of rare diseases, leading to greater support for research funding and policy initiatives.
While challenges remain, the collective efforts of the scientific community, pharmaceutical industry, healthcare providers, patients, and advocates continue to drive momentum toward better diagnosis, treatment, and ultimately, cures for rare diseases.
