Improving care for rare diseases in India

An orphan drug is a treatment designed for a rare disease, or one that has no satisfactory method of diagnosis, prevention or treatment. Although individually uncommon, with an average prevalence of fewer than 40 to 50 cases per 100,000 people, around 350 million patients worldwide are living with a rare disease. 

The low prevalence of these conditions deters pharma companies from investing in drug treatments, leaving the products ‘orphaned’ and unlikely to be developed further or made readily accessible to those who need them. 

Less than 10% of rare disease patients worldwide have received condition-specific treatment, yet their illnesses are typically chronic, progressive and debilitating. Half of rare disease patients are children, a third of whom will die before their fifth birthday. While only 5% of rare diseases have a known cure, many patients can expect an improved quality of life with the right treatment.

Up to 96 million people in India are living with a rare disease, facing limited or non-existent access to treatment. It takes an average of seven years to diagnose a rare disease, after which most treatments are out of reach for the average person or not available in India at all. 

Organization of Rare Diseases India co-founder Prasanna Shirol told The Guardian: “A majority of medication for rare diseases is exorbitantly priced and none is manufactured in India.”

India has the dubious honour of bearing perhaps the most significant rare disease burden in the world. 

This is in part due to being the second-most populous country in the world, but also because around 80% of rare diseases are genetic in origin.

India has a high prevalence of consanguineous and endogamous marriages – unions within extended families or from the same narrow social group, respectively – in some population clusters, which can increase vulnerability to genetic disorders due to a lack of genetic diversity.

Alongside this, access to prenatal diagnostics, genetic counselling and newborn screening is limited. 

While these are fairly standard parts of pregnancy and neonatal care in the US and UK, particularly when it comes to high-risk cases, they are unavailable in the majority of government-run hospitals in India.

In India, rare diseases are classed in three categories – diseases requiring one-time curative treatment, diseases that need long-term treatment where the cost is low and diseases that require lifelong treatment where the cost is high. 

Under the Indian National Policy for Rare Diseases 2021, which was notified on 31 March, financial support of up to 2,000,000 rupees (about $27,000) can be provided for the treatment of rare diseases amenable to a one-time therapy, such as an organ transplant. 

This financial aid is available for around 40% of the country’s population, who are eligible under Ayushman Bharat Pradhan Mantri Jan Arogya Yojana, India’s government-sponsored healthcare programme.

The NPRD does not provide any financial support for those who need more long-term, expensive treatments. For these patients, the government intends to set up a crowdfunding platform where volunteers can donate money for their treatment.

This means that, for those who need to access orphan drugs in India, very little help is available from the state. Orphan drugs are very expensive, considering the extensive research involved to develop them versus the small customer base, meaning only wealthier people are able to afford them.

Several groups work to try and bring orphan drugs to those who need them in India.

Sanofi, for example, has run the Sanofi Genzyme humanitarian programme for rare diseases since 1991, when its first treatment for Gaucher disease was made available. 

Since then, it has expanded to support patients with five different lysosomal storage disorders (LSDs) – rare genetic conditions caused by enzyme deficiencies – as well as patients with haemophilia, a rare genetic disorder in which a person’s blood does not clot normally.

Sanofi Genzyme works with local governments, patient associations and humanitarian organisations to bring patients the medication they need and claims to have treated over 3,200 patients in over 100 countries since the programme began. It has reportedly provided over 100 patients in India with free drugs in the past 21 years.

Another charitable access programme for people with LSDs was started by Shire, a company that has since been bought out by Takeda. A total of 236 patients have enrolled with the programme since its inception, 199 of whom were active participants as of August 2019. These 199 patients are spread across 13 countries, including India.

The numbers alone here show that the pharmaceutical industry’s charitable efforts have had a limited impact – patient groups have been the primary contributors to India’s rare disease ecosystem. 

A study in the Orphanet Journal of Rare Diseasesfound that patient groups have played a  significant role in bringing new diagnostics and treatments to India and have raised awareness about RD issues and screening for rare diseases.

Collective approaches have also been used to try to accelerate the diagnosis of rare genetic diseases in India, as well as treatment. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) aims to establish a unique framework around healthcare planning, implementation and delivery specifically catering to rare diseases. 

The network has over 240 clinicians and scientists based at over 70 major medical and research centres. These clinicians can refer rare disease patients for genome sequencing, to characterise and diagnose their condition. 

GUaRDIAN is a research programme and not a clinical service, but it’s still able to have a real-world impact – once a patient has a diagnosis, they can go forward to seek appropriate treatment options. Plus, the information can help the rest of their family and community too. 

Six children from a consanguineous Muslim family belonging to the Nalband community from north India presented to GUaRDIAN a form of leukodystrophy, a group of disorders that cause deterioration of white matter in the brain. 

The network was able to sequence their exome to find a homozygous variation in the MLC1 gene, which was found in all affected members of the family but absent in the unaffected members. 

Three more families in the Nalband community were found to be affected, indicating a founder effect, so an additional 83 community members were screened. Of these people, 24 were found to be carriers of the variant and a further nine were affected. 

To aid the entire Nalband community, a polymerase chain reaction assay for this particular mutation in MLC1 has been developed to help determine carrier status, at an affordable cost.

Despite these efforts, it’s hard to see how anything short of substantial government action will be able to help improve India’s rare disease infrastructure. 

The US and EU have both taken legislative action to ensure better provision of treatment for people with rare diseases, actions which have made clear differences in terms of healthcare access.

In 1983, the US Congress passed the Orphan Drug Act, encouraging the production of orphan drugs by providing financial incentives to pharmaceutical companies and reducing their potential losses in catering to small markets. 

The country has also had an established Office of Rare Diseases since 2002, which has the authority to recommend a national research agenda, coordinate research and provide educational information for healthcare professionals and patients. 

Meanwhile, the EU’s Orphan Medicinal Product Regulation (EC) 141/2000 aims to help stimulate research into rare disease treatment, while the European Project for Rare Disease National Plan has been developed to facilitate the creation of national plans in the region.

Arjun Raghavan, an advocate practising before the High Court of Kerala, writes in Live Law: “To put it pithily, it can be seen that law-based interventions aimed at curbing rare diseases have encouraged the production of orphan drugs and accommodated health care systems to the needs of patients with rare diseases.”