An estimated 96 million Indians are affected by ‘rare diseases’, for which drugs have either not been discovered or, if there is a drug, it is way too expensive. ‘Rare diseases’ (RD) — which affect a small percentage of the population — constitute a major problem in India, and remain lurking under the radar.

There are an estimated 7,000 RDs in the world, but fewer than 5 per cent of these have an approved drug for treatment. Another estimate says there are 450 RDs in India.

The government is seized of the problem but does not have a solution. In 2021, the government came out with a National Policy for Rare Diseases (following an earlier version from 2017), which describes the problem in detail, and speaks of providing financial assistance to the affected and asking Indian research laboratories to engage with RDs. It notes that “for a long time, doctors, researchers and policymakers were unaware of rare diseases and, until very recently, there was no real research or public health policy” concerning RDs.

Noting that fewer than 10 in a hundred patients receive disease-specific treatment, the NPRD document says that for a child weighing 10kg, the cost of treatment could vary from ₹10 lakh to ₹1 crore a year, and the treatment may be lifelong.

Repurposed drugs

The typical approach to RDs among doctors is to either dip into medical literature for a treatment clue or ask colleagues if they have come across something similar. Both approaches are fraught with risks, says Dr Subramanian Swaminathan, Director, Gleneagles Global Hospitals, Chennai. Medical literature only provides information about (the few) cases that were successfully treated.

Two researchers — Dr Khujith Rajueni of the Department of Clinical Pharmacy, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune; and Dr Mohua Chakraborty Choudhury of DST Centre for Policy Research, Indian Institute of Science, Bengaluru — have explored the viability of using repurposed drugs for rare diseases. “Repurposing drugs used for other common conditions has been considered an essential alternative for RDs due to their cost-effectiveness and reduced timeline, resulting in higher success rates than novel drugs,” they say in a yet-to-be-peer-reviewed paper titled ‘Assessing the availability of repurposed orphan drugs in India’, published in the preprint server Medrxiv.org.

(In an email to Quantum, Dr Choudhury cautioned that “the paper is under review and may undergo major changes.)

Drugs used for RDs are known as ‘orphan drugs’. Drugs repurposed for treating RDs are called ‘repurposed orphan drugs’, or RODs. Rajueni and Choudhury have looked at the availability of RODs, their likely uses, and the need for regulations.

Generic giant

The paper notes that India has a vast potential to use RODs as it is the biggest global manufacturer of generic medicines. “Many RODs out of the exclusivity period are possibly manufactured and available in India and used for other conditions,” the authors say. Further, the patent regime in India disallows evergreening of pharmaceutical patents — namely protection of incremental changes in previously approved drugs. This will enable generic manufacture of many RODs in India. There is also a provision for ‘subsequent new drug application’ for approval of an already approved new drug (within four years) with new claims, namely indications, dosage, dosage form, and means of administration.

Which of the generic medicines could be RODs? The Central Drugs Standards Control Organisation (CDSCO) does not give the ‘orphan’ label to any drug. Rajueni and Choudhury picked 1,033 designated orphan drugs from the US FDA list and culled out 279 as RODs. Their investigation showed that 170 of these were in the CDSCO list. They further researched to see how many of the rest were found in other sources such as Indian Pharmacopoeia (IP), the Food Safety and Standards Regulations (2016), and the Ayush ministry website. This led them to another 42. Thus, 212 of the drugs in the FDA list could be RODs in India — the other 67 would need to be imported.

Noting that “there is an absence of a dedicated orphan drug approval system or information portal in India”, the authors say that there has been no study to assess the availability of orphan drugs in India. As such, the information they dredged out could “guide the industry and researchers to identify drug candidates for which generics can be launched in India”.

Dr Swaminathan stresses the need for an international database on RDs and the possible RODs. The work of Rajueni and Choudhury is perhaps the first step in that direction.

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