Rich pickings from orphan drugs

Some terms tend to be misleading, like when they confuse function with cause. Like orphan drugs. The name has a forlorn ring to it and might lead the uninitiated to believe that these are medicines that are abandoned/neglected and have no protection either from the government or the market. But this is the reverse of reality. Orphan drugs, which treat rare and neglected diseases, are the new blockbuster medicines earning their companies billions in profits thanks to generous incentives in the rich world that have facilitated research and manufacture of such treatments. Till the 1980s, there were just a handful of drugs to treat rare diseases, termed orphan diseases by several countries. Today, close to 900 such drugs have been approved in the US, a stunning jump in recent years. What is significant is that last year 52 per cent of the drugs approved by the US Food and Drug Administration (FDA) were treatments for rare diseases, a trend since 2020. Yet, for millions of patients, there is little access to these vital medicines because of a plethora of challenges, not least the cost.

What exactly are rare or orphan diseases? Every country has its own definition, but generally, these are conditions that affect only a fraction of the population. In the US, these are defined as diseases that affect fewer than 200,000 people, while in the EU, they are life-threatening or chronically debilitating conditions that affect fewer than five persons in a population of 10,000. India does not have a numerical definition of any orphan disease for want of data but for regulatory purposes, the Central Drugs Standard Control Organisation considers a drug as orphan if it is for treating a condition affecting not more than 500,000 people. What is clear is that the unmet medical needs of patients with rare diseases worldwide remains huge, especially in India, which has done little to help such patients unlike other countries in the region. New Delhi’s National Policy for Rare Diseases (NPRD) announced in 2021 provides limited financial support to patients of a maximum of Rs 50 lakh per patient. The reach has been severely restricted, benefitting just 1,118 patients even though 63 rare diseases have been notified.

So far, little has been done to incentivise research and development (R&D) of drugs to treat rare diseases, but recently, the government came up with an unusual incentive—and from an unexpected ministry. On World Sickle Cell Day in June, the Union Ministry of Tribal Affairs announced the Birsa Munda Prize —named after the legendary tribal leader who fought for freedom from British colonial rule—to encourage the development of new drugs for sickle cell disease. The prize of up to Rs 10 crore for approved research proposals, is being offered in collaboration with the All India Institute of Medical Sciences that is setting up a Centre for Tribal Health and Research Institute. The prize money may be small by international standards but it marks an important step on hitherto neglected diseases. Sickle cell disease is estimated to affect well over a million people, primarily in the tribal belt, but as with other diseases, India has no reliable data because it has no universal screening programme. A 2021 "Global Burden of Disease" report estimated the burden at 1.2 million. This might mark a new beginning in the battle against orphan diseases, in which India has been lagging. Thailand, for instance, has set up seven Rare Disease Centres since October 2019 under its Universal Health Coverage Scheme. Crucially, there is a patient-supported national registry that has enabled data collection on diseases, unlocking budgets and securing funding.

China, of course, is streets ahead with a series of orphan drug policies aimed at improving drug accessibility and affordability. To promote accessibility, pharma companies are given tax incentives to expedite drug development. Official support comes in several ways. There is guidance for clinical research on rare diseases, and the provision of data protection for a period of six years, along with market exclusivity for a maximum of seven years. All this is in line with what the Orphan Drug Act in the US (1983), the Orphan Drug Regulation in the EU (1999) and others have implemented to spur R&D in orphan diseases—policies that have shown striking results.

Beijing, while following their examples such as exemptions for clinical trials and acceptance of overseas clinical trial data, has also accelerated the drug registration application, review, inspection and approval processes. To widen access and drug affordability, the import value-added tax on rare disease drugs has been reduced. India could benefit from special steps that Beijing has introduced to tackle rare diseases. One such is the setting up a model protection system for patients suffering from rare diseases in several provinces and cities. This covers the provision of special funds, medical assistance programmes and special insurance coverage to reduce the financial burden on rare disease patients, resulting in an increase in the number of orphan drugs thus covered to 95.

In India, there has been no concerted move to treat orphan diseases, either on the part of the government or by the drug industry. Leading pharma players, who are the world’s top generic companies, have shown little inclination to step into this segment because of the tough patent challenges this involves. An exception has been Natco of Hyderabad, which has taken on drug giant Roche on its drug for risdiplam, a prohibitively expensive drug to treat spinal muscular atrophy, a rare genetic disease that affects motor nerve cells in the spinal cord (see "Putting public health before patent rights" Down To Earth, 16-30 April, 2025).

Tight patent protection has helped Big Pharma rake in astounding profits from orphan drugs. Among the top-earning drugs is ibrutinib, whose sales currently total US $13.1 billion. It is used in treatment of several tumours, such as mantle cell lymphoma and chronic lymphocytic leukaemia. Then comes elexacaftor ($9 billion) to treat cystic fibrosis, followed by olaparib ($5.7 billion), which is described as the first-line treatment of breast cancer susceptibility.

Exorbitant drug prices are admittedly the norm these days, but analysts find there is “an unmistakable trend towards higher prices for orphan drugs”. Of the drugs available, one sturdy says 39 per cent cost more than $100,000 annually while the cost of gene and cell therapies are as-tronomical, ranging from $1-3 million. What is the way out? While the Birsa Munda Prize is laudable, the question is: how far will it take us on tackling rare diseases?

This article was originally published in the September 1-15, 2025 print edition of Down To Earth