In a globalized world, just like most products, drugs and medicines are also made for a global patient population. During the recent pandemic, the world saw how India supplied vaccines, medicines and other material to the rest of the globe. However, the manufacturing of drugs is a complex process which involves a series of clinical trials before a drug is finally approved for licensing, manufacturing, distribution and sale. And it is purely a pharma manufacturer’s prerogative to decide on a product and the target market, based on which subjects for clinical trials are selected. Typically for a global product, subjects would be chosen from a range of geographies and populations.

Now a country like India not only has a high disease burden, but also a high rare disease burden, according to estimates. And indeed the government in recent years has sought to formulate a comprehensive policy for rare diseases in the country. However, despite its high rare disease burden, research has pointed out that hardly any Indian patients are included in the international clinical trials for global drug development programs for rare disease patients. This needs to change.

Negligible inclusion of Indians in global clinical trials

Research has pointed out how the participation of Indians has been slim in global clinical trials for orphan drugs. For 63 orphan drugs approved after 2008, there were 202 trials according to US government’s clinical trial registry. Of these, only 9 had been conducted in India, which amounted to a paltry 4.4 percent. In fact, not more than 1% of the remaining 193 trials had included people of Indian origin. Effectively, it was found that the nine studies were related to only six out of 63 drugs.

Extraordinary ethnic diversity of India

India offers a widely diversified ethnic and racial profile of people, which would be an interest to pharma researchers and manufacturers. There are more than 2,000 known ethnic groups, apart from over 700 tribes and other people with shared gene pool from neighboring countries and geographies. And just as some race and ethnic groups may be more pre-disposed to certain diseases and illnesses, some groups may also respond differently to different drugs and lines of treatment. Research has established how genetic variations, differences in environmental exposure and differences in diet and health-related practices are critical to understanding how a certain population group would respond to a line of treatment.

High number of rare disease patients in country

Assuming the estimate that nearly 6-8 percent population of a country is affected with rare diseases, this amounts to between 81 and 108 million people in a population of at least 1350 million. These are staggering numbers. By not including Indian patients in clinical trials, global pharma companies are possibly overlooking the health and lives of nearly 80-100 million people afflicted with rare diseases. These numbers are more than double (or even more) of what they are in Europe and the US. Although in a world which has nearly 7,000 rare diseases, only about 450 rare diseases have been recorded in India based on data from tertiary care hospitals. Yet even 450 is not an insignificant number. And this is in the absence of proper epidemiological data. If systematic epidemiological studies would be undertaken, the numbers and incidences would shoot up even more within the country.

Make a start with existing diseases at least

Until the time India bolsters its rare disease surveillance and improves epidemiological data collection and analysis, global pharma companies could make a beginning with at least the already prevailing rare diseases in the country. Some of the existing rare disease conditions found in the country include Haemophilia, Thalassemia, Sickle-cell Anaemia and Primary Immuno Deficiency in children, auto-immune diseases, Lysosomal storage disorders such as Pompe disease, Hirschsprung disease, Gaucher’s disease, Cystic Fibrosis, Hemangiomas and certain forms of muscular dystrophies.

Possible challenges for global pharma companies

There is no doubt that there would be challenges along the way for companies. Firstly, the classic dilemma between commercial and ethical would definitely play on their minds. For a company to consider including Indians in global clinical trials for a rare disease medicine, it would have to assess the pros and cons while exploring the over-all business feasibility for the Indian market. Typically, the cost of a clinical trial for a new drug for rare disease would be at least $ 200 to 300 million – even with a small sample of 100-150 subjects. If the size of the sample is increased, the cost could go up even higher. Another related challenge would be in terms of the uncertain business environment for the manufacturer in the post-approval phase. Typically, in developed countries, once a drug is approved, the government takes over the costs of the treatment for patients who continue to get treatment from the company. There is no such arrangement in India making it a deterrent for companies. Then data security would be another big challenge. India has very limited number of good clinical practice sites where fail-proof clinical trials for rare disease medicines can be conducted. Furthermore, there is also a chance of pilferage of sensitive proprietary information resulting in half-baked and unauthorized medicines coming into the market.

Despite the challenges, global pharma companies could consider including more of Indian participants in their clinical trials for orphan drugs. In addition to the unavailability part, given the high cost of treatment when available, the inclusion of Indian patients would at least provide patients the rare opportunity to get access to treatment for at least during the time of the trial. Also, given that 80% of rare diseases are genetic in origin, they impact children the most. So, the inclusion of Indians in global clinical trials for rare diseases would not only address the needs of Indian patients but also make the entire drug research and discovery process more scientifically valid and robust. Of course, the commercial interests of companies could be addressed by the government stepping in just as other governments do in developed countries. This ensures that the patient continues his treatment post-approval while the companies’ commercial interests are taken care of.