By Harsha Rajasimha
Patients with rare diseases often lack adequate access to treatment due to a lack of awareness and medicines. Rare diseases include congenital malformations, autoimmune disorders, lysosomal storage disorders, thalassemia, muscular dystrophies, some forms of cancer, and certain endemic infectious diseases with a very low prevalence, among others. About 80% of rare diseases have a genetic cause.
There is no standard global definition of a rare or orphan disease. In the U.S., a disease is defined as rare if it affects fewer than 200,000 people, while the threshold is 50,000 in Korea and 2,000 in Australia. Per the World Health Organization, a rare disease has a frequency of 6.5–10 per 10,000 persons.1 In India, there is still no national definition of a rare disease, as the country lacks sufficient epidemiological data to define a rare disease. However, the National Policy for Rare Diseases has identified three groups of rare diseases based on their treatability, treatment availability, and status. The Central Drugs Standard Control Organization (CDSCO) considers any drug for a condition affecting fewer than 500,000 Indians as an orphan drug for the purposes of regulatory review.
Rare diseases in India and beyond
Of the ~10,000 rare diseases identified globally, ~450 have been reported among the Indian population.2 Extrapolation from global data suggests that the country could have 70–96 million people living with rare diseases.4 In 2021, the Indian Council of Medical Research (ICMR) initiated a hospital-based National Registry for Rare Diseases to gather much-needed epidemiological data on rare diseases in the country.
The diagnosis of a rare disease in India takes an average of seven years from the onset of symptoms, and many cases likely remain undiagnosed.4 Many patients and healthcare providers lack awareness of rare disease. The Ministry of Health and Family Welfare in India has designated 8 to 10 Centers of Excellence (CoE) to manage rare diseases diagnosis, prevention, and treatment. The CoEs have been allocated funding of up to INR 50 million ($612,000) to acquire and set up equipment, and they are exempt from basic customs duty for medicines used for treatment of rare diseases.7 The Indian government has also allocated INR 5 million (about US$61,200) as a one-time grant per patient for treatment, to be given to the appropriate CoE.
These amounts are grossly inadequate given the typically high expense of treatments for rare diseases and the costs of acquiring equipment. Moreover, many patients require lifelong administration of antidotes, supportive medication, enzyme replacement therapy, high-cost procedures such as hematopoietic stem cell transplant (HSCT), or organ transplantation. These treatments, when available, can cost anywhere between INR 1 million and 25 million, pushing families into poverty.3 The families are also drained physically and emotionally, as treatment and support are often required for a lifetime.
With a population of 1.3 billion, India has a high burden of rare diseases due to a high birth rate, high consanguinity rate, and other socio-economic factors. Further, the Indian diaspora is the largest in the world, comprising more than 4.2 million people in the U.S. alone.
Inclusion is important for the generalization of study outcomes
Although India is home to an ethnically diverse population, and is home to about a quarter of the world’s people, most clinical trials do not include an adequate number of participants from the country. Less than 2% of global clinical trials have any study sites in India.
Given the small number of rare disease patients within a particular country or geography, it’s challenging to enroll participants in rare disease trials. Frequently, rare diseases are severely debilitating, limiting the capability of potential participants to travel to a study site. And without a diverse base of study participants, researchers lack representative data on disease progression and treatment efficacy.
As consequences of the failure to include Indian patients in studies, not only do Indian patients miss out on opportunities to avail themselves of clinical research as a care option, but drugs are eventually approved based on the safety and efficacy data from mostly non-Indian patients. A majority of these orphan drugs are discovered and developed in the Western world, which is home to less than 10% of the global population, and inefficiencies and ineffectiveness continue to haunt the industry. Launch strategies for orphan drugs typically pursue approval in the U.S. first, then from the European Medicines Agency, and then in Japan, leaving a long gap before these treatments are available, accessible, and affordable to patients in India and other emerging markets. Most patients in India receive functional therapies only to alleviate symptoms due to the lack of specific targeted treatment. The rarity and complexity of rare diseases make inclusion of Indians and other underrepresented ethnic minorities essential.
The Need for Cross-border collaborations to tackle rare diseases
Out of about 10,867 rare diseases identified globally, only about 8% are treatable.6 Thus, even with more than 1,080 orphan drugs approved by the U.S. Food and Drug Administration, the majority of people with rare diseases are still living without any approved therapy for their condition. With the Indian government’s recent allocation of funds for the treatment of patients with rare diseases, biopharmaceutical companies should rethink their clinical trials and global launch strategies. With genetic testing becoming increasingly common in India, manufacturing and administration of targeted or precision therapies are already growing in the country.
The need of the hour for rare disease patients in India and of the Indian diaspora is for all stakeholders of the regulated healthcare and life science ecosystem to collaboratively raise awareness about rare diseases and the related clinical trials that are being conducted, and thereby increase participation in trials. Furthermore, it is imperative for patient communities, policymakers, and physician-researchers, to advocate and incentivize biopharmaceutical companies to substantially increase investments in the development of diagnostic tools and drugs for rare diseases. As part of this effort, the nonprofit I lead, Indo US Organization for Rare Diseases (IndoUSrare), advocates that orphan products developers include global (as opposed to U.S. or E.U. only) rare disease incidence and prevalence data in their applications for investigational new drug status, biologic license application, and orphan designation.
Most existing databases for rare disease biomedical research are curated in the U.S. and E.U., and hence fail to represent global diversity. In collaboration with RARE-X, a collaborative platform for global data sharing and analysis to accelerate treatments for rare disease, we at IndoUSrare conducted a feasibility assessment of patient-owned registries in India. Inclusive patient registries and natural history studies are essential prerequisites for rare disease therapies to be developed. There is an urgent need to create such registries in India and for the Indian diaspora to be included in existing and new global registries. As India and other countries draft health data privacy regulations, the needs of rare disease research and development, including the cross-border nature of rare disease patient registries, should be considered.
In summary, to accelerate orphan drug development, global strategies are critical. At IndoUSrare, we are building a team of committed individuals with relevant expertise to advocate for global inclusion in rare disease trials and to ensure equitable access to life-saving therapies for everyone who needs them. Through online and in-person events such as the upcoming BRIDGING RARE Summit in October 2023, we are catalyzing cross-border collaborations and networks connecting stakeholders of rare diseases in densely populous regions such as the Indian subcontinent with their counterparts in the U.S. We believe that these collaborations are needed to close critical gaps, accelerate innovation to test new concepts, develop solutions for rare diseases, or extend the capabilities of the research networks composed of clinical research organizations, sponsors of clinical trials, and health systems.
- Organization for rare diseases India (ORDI) – addressing the challenges and opportunities for the Indian rare diseases’ community
- Rare diseases: Small numbers, huge burden
- Rare disease patients in India are rarely involved in international orphan drug trials
- NATIONAL POLICY FOR RARE DISEASES, 2021
- 7 Rare Diseases That Can Now Be Treated
- Initiatives by the Government for treatment of rare diseases
Harsha Rajasimha is the founder and chairman of IndoUSrare. IndoUSrare is a humanitarian non-profit 501(c)(3) tax-exempt public charity organization based in the U.S. 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, the regulatory sector, 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 U.S. The organization’s goal is to improve the diversity of clinical trial participants, accelerate research and development, and improve equitable access to life-saving therapies for diverse populations of rare disease patients. Visit indousrare.org