THERE ARE APPROXIMATELY 7,000 known rare diseases, often referred to as ‘orphan diseases’, affecting around 4 to 6 percent of the world’s population, that is nearly over 400 million people of the 8.2 billion people in the world. 75 percent of rare disease patients are children. In the United States (‘USA’), a disease is classified as ‘rare’ if it affects less than 200,000 individuals. In the European Union (‘EU’) they are defined as affecting less than 1 in 2,000 people.
Because rarity is defined proportionally, even a small percentage translates, in a country of India’s size, into hundreds of thousands of affected individuals. Merely because they represent a small percentage does not mean their concerns and health can be ignored.
Why rare disease drugs remain out of reach
Rare diseases include Hutchinson-Gilford Progeria Syndrome, a genetic disorder causing rapid aging in children; and Spinal Muscular Atrophy, caused by a mutation in the SMN1 gene that results in insufficient production of the Survival Motor Neuron protein. The deficiency progressively weakens the muscles of the spine, impairing posture and breathing, and is ultimately fatal.
An estimated 3,112 infants with SMA are born in India every year. A medical genetics clinic covering Uttar Pradesh (home to 16.5% of India's population as per the last census) and neighbouring states found an SMA carrier frequency of 1:38 among individuals with no prior family history of the disease, a finding with significant implications for policy.
It is well-known that medicines for treating rare diseases are not a priority for the pharmaceutical industry. The few treatments that do exist are largely developed by Western and Japanese Multi-National Companies(‘MNCs’). On the pretext of high costs of discovery and development costs, these companies price their drugs at levels entirely beyond the reach of ordinary patients..
Western countries and Japan cushion their citizens through national health systems that cover rare disease treatments. In developing countries, no such safety net exists which makes access to costly rare disease medicines a persistent and often insurmountable challenge.
India’s policy on rare diseases
India is a good example of a developing country on what are the challenges for rare diseases and how they can be overcome.
The Government of India introduced National Policy for the Treatment of Rare Diseases in 2017, expanding the same in 2023. At the instance of the Delhi High Court in Arnesh Shaw v Union of India, the National Policy for Rare Diseases was notified by the Government of India on 23 March 2021 (‘NPRD 2021’). Currently, most major rare diseases are already covered under that policy. The NPRD, 2021, categorizes rare diseases into three groups:: - Group 1: Disorders that can be cured with one-time treatments, such as certain Lysosomal Storage Disorders and immune deficiency disorders; Group 2: Diseases requiring long-term or lifelong treatment with relatively lower costs, such as phenylketonuria and homocystinuria and Group 3: Disorders for which definitive treatment exists but with high costs and lifelong therapy, such as Gaucher Disease and Duchenne Muscular Dystrophy.
Under the NPRD 2021, the government funds the procurement of medicines for rare disease patients. The central impediment, however, is the per-patient expenditure ceiling. Initially set at Rs. 20 lakhs (USD 22,760), this ceiling was raised to Rs. 50 lakhs (USD 56,900) again at the Delhi High Court’s direction in Master Arnesh Shaw.
Rare disease patients and the Courts
Rare disease patients across India have been compelled to approach High Courts seeking directions to compel the government to provide treatment. Most of these cases were filed in the Delhi High Court. Other cases were filed in other High Courts, including Kerala, by a patient affected by SMA.
For some conditions, Rs. 50 lakhs is adequate. For Group 3 diseases, it does not cover even a single year of treatment. In Master Arnesh Shaw, the Delhi High Court directed the Union Government to encourage indigenous production and directed that the Rs. 50 lakh ceiling for Group 3 diseases must remain flexible, to be raised case by case by experts in the National Rare Diseases Committee (‘NRDC’), the body tasked with implementing the NPRD 2021..
The Government challenged this direction before the Supreme Court, arguing that a court cannot direct the State to act contrary to its own policy. The Supreme Court stayed the order of the Delhi High Court on the ceiling.
There are three drugs in the world for treating SMA, Spinraza manufactured by Biogen, Zolgensma manufactured by Novartis and Risdiplam manufactured by Hoffman La Roche. Risdiplam was issued a patent in India by the Patent Controller and granted approval from the Drug Controller General of India to market it in India. The price fixed by Roche to sell the Risdiplam in India was Rs. 72 lacs (USD 85,680). Barring billionaires, very few people in India can afford it. Since the drug is required lifelong, State funding covers, at best, a single year of treatment.
The case of Seba, a young girl from Kerala, illustrates what this gap means in practice.Seba, diagnosed with SMA, approached the Kerala High Court, which directed the Union Government to fund her Risdiplam treatment, a direction the government complied with. As her funding neared exhaustion, she returned to the Kerala High Court seeking a direction that treatment continue beyond the Rs. 50 lakh ceiling. The Court agreed and directed that the treatment should continue beyond Rs. 50 lacs. Basing themselves on the stay order passed by the Supreme Court in Master Arnesh Shaw, the Union Government challenged that direction of the Kerala High Court in the Supreme Court and obtained a stay. Seba would be without treatment beyond the one-year period.
In her petition, Seba had pointed out that in China, the Government, and in Pakistan, NGOs, had negotiated with Roche, the patent holder for Risdiplam. The relative prices negotiated were as follows:-
The Government did not make any effort to negotiate with Roche, until the negotiations and the resultant prices in China and Pakistan were made available in the Delhi High Court. Negotiations took place after that. However, the price agreed has not been disclosed. Whatever was agreed, it remains above Rs. 50 lakhs per year.
When this was brought the Supreme Court’s attention, it issued notice to Roche, the manufacturer of Risdiplan, which agreed to continue the treatment of Seba for another year. Several other applicants have filed applications in the Supreme Court to be heard on the question of the Rs. 50 lakh ceiling.. The Supreme Court is to hear that issue soon.
Patent infringement in the Delhi High Court
In the meantime, Natco, a generic drug company got approval to manufacture a generic version of Risdiplam in India. The cost of the generic equivalent of Risdiplam is available from Natco at almost Rs. 5-6 lakhs per patient per year, roughly 90 percent0% cheaper than Roche’s Risdiplam At that price, the government's Rs. 50 lakh ceiling would fund approximately a decade of treatment.
Since the drug was patented in India by Roche, it moved an infringement action against Natco before the Delhi High Court. Seba intervened in the matter.
Seba intervention brought to light the stark disparity in Roche's pricing across jurisdictions. In China the Government had negotiated the price with Roche at USD 545; in Pakistan, NGOs had secured USD 500 for a patient of 20 kgs per year. In India, Roche was charging USD 7,200 for the same drug, for the same weight category.
Roche also claimed, without substantiation, that the cost of discovering and developing the drug was approximately USD 2 billion. Indeed, patents contribute significantly to the exorbitant cost of drugs for rare diseases. Many drugs are, in fact, developed by smaller companies that are acquired by bigger ones and taken to clinical trials. Big companies often hold these patents despite not bearing initial costs of developing several candidate drugs. The figures these companies have been giving out for years are an exaggeration. An analysis by Jamie Love of Knowledge Ecology International found that Roche's actual cost of discovering and developing Risdiplam in the United States was no more than USD 20 million.
A study by Dr. Melissa Barber further found that the actual cost of manufacturing a generic version of Risdiplam does not exceed Rs. 3,024 (USD 35.99) per year.A single judge of the Delhi High Court refused to grant Roche an injunction against Natco. Roche appealed to the Division Bench, which dismissed the appeal. Roche then filed a Special Leave Petition before the Supreme Court, which rejected it at the threshold, finding no reason to interfere with concurrent findings of two courts.
Compulsory lLicensing of such drugs could have helped in cost reduction much earlier. However, in India, the compulsory licensing provision has been invoked only once, when Natco Pharma, secured the permit to manufacture Nexavar, a cancer drug made by the German MNC Bayer, in 2012. The government's reluctance stems in part from fear of trade repercussions. The United States has placed India on both its Special 301 watch lists.
In her writ petition before the Kerala High Court, Seba had also sought the issuance of a compulsory licence for Risdiplam, in addition to her prayer for treatment funding. The Union Government, apart from challenging the interim order of the Kerala High Court to give Risdiplam to Seba beyond the one year, also applied for transferring that writ petition to the Supreme Court.
Seba has since filed an application before the Supreme Court seeking a direction that the Government of India bulk purchase Natco’s generic from Natco and distribute it to all SMA patients in the country. This would reduce costs dramatically for the exchequer. Surprisingly, till now, the Government has not responded favourably.
