By Aditya Pai, VP Corporate and Business Development, MedGenome Inc, USA.
February 28th is Rare Disease Day. It is a day where the realities of Rare Diseases need to be highlighted for all health industry stakeholders; to celebrate the progress that has been made as well as to inspire us for the challenges that lay ahead.
Rare diseases are defined as those conditions thar affect fewer than 1/ 1200 people. More than 300 million people globally are affected by a rare disease1,2. Patients and families with rare diseases are one of the most underserved communities in medicine today. There are 7000 + documented rare diseases, yet for the most, a cure or treatment is not available3. Only 5% of rare diseases have an approved treatment. Most rare diseases get misdiagnosed or remain undiagnosed resulting in complex testing and clinical odysseys. This is often due to the variability in symptoms from disease to disease for also for the same disease from person to person. 70% plus of rare diseases are seen in children while greater than 72% are genetic in origin.
There are three key challenges with rare disease research: 1. Diagnosis 2. Treatment 3. Equity
- Diagnosis: Especially in neonates, the emotional trauma caused to new parents with an undiagnosed rare disease is heartbreaking. With costs of sequencing falling, in 2022, it is possible to perform far more elaborate next generation sequencing (NGS) than even five or ten years ago. Whole genome sequencing (WGS) or whole exome (WES) / clinical exome sequencing (CES) has been proven to detect with more sensitivity and specificity previously undiagnosed rare diseases. For example, in a 2020 UK study, WGS data for 13,037 participants, of whom 9,802 had a rare disease was analyzed. A genetic diagnosis was provided to 1,138 of the 7,065 phenotyped participants. 95 Mendelian associations between genes and rare diseases were found. At least 79 of these were confirmed to be etiological. Further, a 2021 UK study for whole genome sequencing for neurological patients with repeat expansion disorders (e.g., Fragile X syndrome) showed high sensitivity and specificity, and led to the identification of neurological repeat expansion disorders in previously undiagnosed patients. The use of NGS – in particular WGS has proven to be invaluable in diagnosis.
- Treatment: Rare disease drug development has unique challenges. Finding patients for clinical trials, the small number of patients affected, as well as the heterogeneity of rare diseases and the way they progress makes clinical trial design and participation a challenge. Understanding the natural histories of disease can play a vital role in drug development especially when designing meaningful end points and patient inclusion / exclusion criteria. In the USA, government has provided various incentives to drug manufacturers. The results of a 2020 CDER report4 showed that of the 53 novel drugs approved in 2020, 58% were for rare diseases demonstrating the interest of pharmaceutical and biotechnology companies.
- Equity: Not everyone can afford whole genome sequencing or any form of genetic testing or treatments that are costly. This can lead to large inequities in diagnosis, treatment and ongoing care globally. The financial and emotional cost to families affected by rare disorders can be enormous as a result of such inequities.
A Call to Action:
- More affordable WGS/WES/CES, its interpretation with appropriate genetic counseling and care key to stymie long and complex diagnostic odysseys.
- Pharmaceutical companies need to continue to adopt global strategies to not only understand the natural history of specific rare diseases, but also include more countries to recruit patients for trials. For example, India and South Asia have the world largest population of people affected by rare and inherited disease. This is highly relevant, considering the large number of rare diseases and the small global pool of potential patients available for clinical trials.
- Health policy must account for equitable access to diagnosis, treatment and care for rare disease populations. While these will vary by country, its essential to start developing a policy for rare diseases, orphan drugs and their cost-effective access.
Rare Disease Day 2022 represents another opportunity to remind ourselves of the work that remains. At MedGenome, we have formed a strategic alliance with Emmes across six rare disorders with the goal of expanding and accelerating Rare Disease research and development. Our partnership will combine patients’ genomic, phenotypic and epidemiological data into custom rare disease registries. MedGenome in India routinely offers CES and has solved many undiagnosed conditions successfully. Through our clinical collaborators, we continue to highlight the unique aspects of Indian genomes in the understanding the natural history and heterogeneity of rare diseases as well as the role they can play in global rare disease clinical trials.
- 1 Am J Med Genet A. 2019;179(6):885–892. http://doi.org/10.1002/ajmg.a.61124.
- 2 Eur J Hum Genet. 2020;28(2):165–173. https://www.nature.com/articles/s41431-019-0508-0
- 3 Ibid.
- 4 https://www.fda.gov/media/144982/download
#Rarediseases, #Rare disease research, #diagnosis, #treatment, #equity, #next-generation sequencing #Whole genome sequencing #clinical trial design