Clinical Studies of Rare Diseases
Without true international collaboration, there will continue to be gaps in global patient registries and incomplete data due to a lack of multicultural sampling of patients, which decelerates the development of orphan pharmaceuticals and treatments
HERNDON, Va. (PRWEB)
August 01, 2023
There are globally inconsistent definitions of what constitutes a rare disease. According to the Orphan Drug Act enacted by the U.S. Congress in 1983, a rare disease is a medical condition that affects fewer than 200,000 people.(1) A comprehensive 2022 study conducted by RARE-X concluded that there are 10,867 orphan, aka rare diseases, including genetic and non-genetic diseases, rare cancers, and diseases that are either poorly defined or not currently recognized in the major databases.(2) There are 459,912 clinical trial studies currently being conducted in the U.S. and 221 countries worldwide.(3) Yet, there continues to be underrepresentation in critical diversity categories, including age, gender, race, ethnicity, culture, and geography. International orphan drug clinical trials scarcely involve rare disease patients in Asia and India. According to the most recent estimate in 2020, about 258 million people in the Asia Pacific region were estimated to be impacted by rare diseases, with nearly half being children.(4) India comprises one-third of all rare disease cases worldwide.(5) Dr. Harsha Rajasimha is the Founder and Executive Chairman of the Indo-US Organization for Rare Diseases (IndoUSrare), a not-for-profit organization that seeks to bridge the gap that exists in the world when it comes to rare diseases.
Dr. Rajasimha notes, “Massive disparities exist between the Eastern and Western Hemispheres regarding access to diagnostics, clinical trials, drugs, medical devices, therapies, and cures. There is a disproportionate prevalence of certain rare diseases across different countries in the world. Without true international collaboration, there will continue to be gaps in global patient registries and incomplete data due to a lack of multicultural sampling of patients, which decelerates the development of orphan pharmaceuticals and treatments.”
The Public Library of Science (PLOS) Global Public Health published a research study to assess the involvement of rare disease patients in India in international clinical trials.(6) Researchers investigated Indian patients’ participation in international trials for orphan drugs and discovered that only 9 out of 202 trials registered in the U.S. took place in India. Taking the Indian diaspora into consideration, of the remaining 193 trials, approximately 1% recruited patients of Indian origin. It has been clinically proven that different ethnic and racial groups respond differently to specific drug treatments. India consists of a large ethnically diverse population, and their exclusion significantly limits the implications of diversity on trial outcomes.
A study published in Nature Genetics(7) reveals potential medical predispositions among various South Asian subpopulations due to genetic isolation caused by endogamy (the tradition of exclusively marrying within the confines of a local community, clan, or tribe) and cultural practices. For example, in specific states of Southern India, anesthesiologists inquire about Vysya heritage before surgery due to some fatal responses to muscle relaxants observed among individuals with Vysya ancestry.
The Nature Genetics study reveals that the South Asian population, consisting of over 1.5 billion people, is not a homogeneous entity but rather comprises thousands of distinct groups, including various castes and subcastes. These groups have been reinforced by cultural customs that encourage marrying within their own communities. Although there have been some recent shifts towards inter-caste and inter-subcaste marriages, especially in urban areas, gene flow between these populations has remained limited for thousands of years.
Over a span of more than 15 years, researchers have gathered DNA samples from over 2,800 individuals representing 260 South Asian groups. The study identified certain groups with strong founder effects, a reduction in genetic diversity that takes place when a small group from a larger population establishes a new population, leading to a reduction in genomic variability. This condition increases the risk of recessive diseases within these groups. Studying these distinct South Asian groups offers valuable insights into both rare and common diseases, presenting significant opportunities for genetic research.
The study also highlights the vulnerability to rare genetic diseases among residents of India and other South Asian nations; using genomic analysis, this research holds the promise of pinpointing and proactively preventing disorders that are specific to particular populations. While some South Asian-specific diseases have been previously identified, the root genetic causes of most of these conditions have remained largely unknown. The occurrence of population-specific, recessive diseases in the region has been amplified by the founder effect phenomenon, which arises when a small group of ancestors gives rise to a large number of descendants.
Spinocerebellar ataxias (SCA) are neurological disorders that result in abnormalities in gait and movement. This rare genetic condition has an estimated prevalence of around 2 cases per 100,000 people. SCA type 3, also called Machado Joseph Disease (MJD), is common worldwide but rare in India. However, in the district of Buldhana, India, several families from a close-knit community were affected. Genetic analysis confirmed SCA3 in these families, revealing a significant burden of the disease. The impact in this single village surpassed the total cases seen at the All India Institute of Medical Sciences (AIIMS) in the last two decades.(8)
Among rare diseases reported in India are hemophilia, thalassemia, sickle cell anemia, and primary immunodeficiency in children. Additionally, there are autoimmune diseases, lysosomal storage disorders such as Pompe disease, Hirschsprung disease, Gaucher’s disease, cystic fibrosis, hemangiomas, and certain forms of muscular dystrophy. The prevalence of rare diseases such as sickle cell anemia, ALS, muscular dystrophies, cystic fibrosis, and others are not homogeneous across the world or among all races and ethnicities. Sickle cell anemia, for example, is rare in the US but common in Africa, the Middle East, India, and other countries.
Recently, the Prime Minister of India launched the mission to eradicate sickle cell anemia, inviting all stakeholders to unite in the battle against this deadly disease that predominantly affects tribal communities in India. Earlier this year, Gautam Dongre from the National Alliance of Sickle Cell Organizations (NASCO) joined 40 other patient foundation members of the IndoUSrare patient alliance to maximize access to numerous investigational medicines under development by the US biopharmaceutical industry. Cystic Fibrosis and ALS are more common among rare genetic diseases in the US but rarer in India and elsewhere. This makes the distinct call for global collaborations critical in the research and development of diagnostics and therapies for all rare diseases.
As per the Ministry of Health and Family Welfare’s data,(9) India has documented approximately 450 rare disease types to date (contrast this with the 10,857 rare diseases acknowledged in the Western world). Based on estimates, half of the new cases occur in children, resulting in 35% of deaths before one year of age, 10% between the ages of one and five years, and 12% between five and 15 years.
The World Health Organization (WHO) defines these diseases as debilitating, lifelong conditions with a prevalence of less than one per 1,000 individuals. They encompass autoimmune disorders, congenital malformations, inherited cancers, and certain endemic infectious diseases with extremely low prevalence rates.
Managing rare diseases in the Asia Pacific region poses unique challenges due to socioeconomic disparities, limited research, expertise, and health policies specific to rare disease patients. The region also faces low medical awareness and a lack of momentum in recognizing and addressing the unmet needs of these patients. Additionally, the paternalistic health systems in the region further exacerbate these issues, often neglecting the voices and concerns of rare disease patients.(10) Participating in randomized controlled trials (RCTs) also burdens patients with psychological, physical, and financial challenges. Factors like poor trial information and disorganized follow-ups exacerbate the ordeal.(11)
India’s Ministry of Health and Family Welfare established the National Policy of Rare Diseases (NPRD) to increase indigenous research and local medicine production, lower the cost of treatment, promote early detection screening and prevention, and provide financial support for those suffering from rare diseases; however, the NPRD program has been plagued by ongoing funding and implementation challenges.(12)
IndoUSrare facilitates global collaboration among all stakeholders to accelerate research for rare diseases and enhance the development of efficient treatments. Their focus is on promoting equal opportunities, inclusiveness, and the availability of life-saving therapies to patients worldwide, regardless of age. The successful regulatory approval of treatments hinges on the essential partnership between patient groups, academic researchers, and industry partners.
The IndoUSrare Corporate Alliance is a coalition of biopharmaceutical, diagnostics, medical device, and other companies in the life science industry devoted to advancing orphan product development. Their shared goal is to educate, empower, and advocate for patients with rare diseases in the United States, India, and around the world, foster collaboration, and fill critical gaps to hasten diagnostics and therapies. IndoUSrare is working to create partnerships among different stakeholders, pooling resources across borders for affordable research and development.
Dr. Rajasimha explains, “Yes, there are umbrella organizations around the globe focused on rare diseases within their respective countries, but the key here is ‘within their own countries.’ The news publicizes their individual efforts, but very little focus is directed to true international collaborations — those that go beyond lip service and national borders and create a bridge between people, cultures, and medical science to find therapies and cures. This is the scenario in which IndoUSrare defined its mission and sprang into action — to make a difference in the world.”
To join the global crusade, Register Now for the Indo US Bridging RARE Summit 2023.
Connecting the Global Rare Disease Community
October 29–30, 2023
George Mason University, Arlington, VA, USA
About IndoUSrare
IndoUSrare is a humanitarian nonprofit 501(c)(3) tax-exempt public charity organization based in the United States. Founder and Executive Chairman Dr. Harsha Rajasimha, who lost a child to a rare disease in 2012, has been a rare disease advocate for more than 10 years. To address the unmet needs of diverse patients with rare diseases globally, the leadership team comprised of experienced professionals from research, advocacy, regulatory, and drug development seeks to build cross-border collaborations connecting stakeholders of rare diseases in low- and middle-income regions such as India, with their counterparts and clinical researchers in the United States to improve the diversity of clinical trial participants, accelerate research and development, and improve equitable access to life-saving therapies to diverse populations of rare disease patients. Visit https://indousrare.org.
References:
1. Commissioner, O. of the. (n.d.). Rare diseases at FDA. U.S. Food and Drug Administration. fda.gov/patients/rare-diseases-fda.
2. Rare-X releases new report that uncovers large number of previously uncounted rare diseases. RARE. (2022, June 7). rare-x.org/blog/2022/06/07/rare-x-releases-new-report-that-uncovers-large-number-of-previously-uncounted-rare-diseases/.
3. Trends, charts, and maps. ClinicalTrials.gov. (n.d.). classic.clinicaltrials.gov/ct2/resources/trends.
4. Carter, J. (2023, February 14). Rare disease care across asia pacific. Sandpiper. sandpipercomms.com/health/rare-disease-care-across-asia-pacific/.
5. Patel, M. and S. (2022, July 18). Rare diseases in India: “orphan” no more? ORF. orfonline.org/research/rare-diseases-in-india-orphan-no-more/.
6. Chakraborty, M., Choudhury, M. C., Chakraborty, I., Saberwal, G. (n.d.). Rare disease patients in India are rarely involved in International Orphan Drug Trials. PLOS Global Public Health. journals.plos.org/globalpublichealth/article?id=10.1371%2Fjournal.pgph.0000890.
7. Nature Publishing Group. (2017, September 1). Ancestry-inspired Genomic Health. Nature News. nature.com/articles/ng.3953.
8. Uncovering the hidden burden of rare genetic diseases in India. Genomics and other omics tools for enabling Medical Decisions (GOMED). (n.d.). gomed.igib.in/impact-stories/uncoveringthehiddenburdenofraregeneticdiseasesinindia.
9. Rare diseases need not be neglected anymore. BioSpectrum India. (n.d.). biospectrumindia.com/features/73/22713/rare-diseases-need-not-be-neglected-anymore-.html.
10. Jain, R. (2020, July 20). Rare diseases in Asia and the Pacific must be tackled too. Asia Pathways. asiapathways-adbi.org/2020/07/rare-diseases-asia-pacific-must-be-tackled-too/.
11. Naidoo, N., Nguyen, V. T., Ravaud, P., Young, B., Amiel, P., Schant; eacute;, D., Clarke, M., Boutron, I. (2020, January 20). The research burden of randomized controlled trial participation: A systematic thematic synthesis of qualitative evidence – BMC medicine. BioMed Central. bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1476-5.
12. Rare disease policy: Need of the hour. Times of India Blog. (2023, April 24). timesofindia.indiatimes.com/blogs/voices/rare-disease-policy-need-of-the-hour/.
