India’s Ignoring Its Rare Disorders and Their Orphan Drugs Led to the Thalassaemia Crisis


I was facing a life-and-death situation two weeks ago. I nearly ran out of a life-saving medicine and I was wondering what to do.” Thus began a desperate online petition by a thalassaemia patient, Namitha Kumar, research director of the Centre for Health Ecologies and Technology (CHET) at the Indian Institute of Science, Bengaluru. The petition was tagged to draw the attention of health minister J.P. Nadda to the shortage of the injectable drug Desferal in early September.

The supply has since been restored. But, says Kumar, her fresh stock will last her for just another month, and it is unclear whether there will be an assured supply of the drug after. “The drug supply has been irregular for the past one year,” she told The Wire. “This August, we did not get the drug in Bengaluru. It has also run dry in Delhi, Mumbai, parts of Assam, Gujarat and Maharashtra.

And on September 5 and 6, Vishwanath Muralidharan, secretary of the National Platform for the Rights of the Disabled , wrote to Ananth Kumar, the minister for chemicals and fertilisers, and Nadda requesting that the government ensure a steady supply of Desferal for thalassaemia patients. “Even thalassaemia societies in some cities, who buy it directly from the manufacturer and pass it on to patients, are left without stocks now.”

The letters sought “the urgent intervention” of the two concerned ministers to ensuring an adequate supply of the drug to those in need. However, Novartis, the only company that makes the drug in India, says that “there are sufficient stocks of Desferal to meet the needs of patients. The product is not manufactured locally and additional supplies are expected in the third week of September. Until then we are managing (an) existing inventory so that no patient goes without Desferal.”

Be that as it may, the incident brought into focus the problems of patients with thalassaemia, which in turn is among several rare disorders in India, with relatively fewer patients. This is in contrast to infectious diseases like tuberculosis, malaria, and dengue. And drugs to treat rare disorders are dubbed ‘orphan drugs’ that neither the government nor the domestic pharmaceutical industry is interested in, explained Kumar.

Adding to the problems of disinterest are issues of affordability and access to affordable medicines. For example, Kumar is among 5% of an estimated 100,000 thalassaemia patients in India who can afford to buy the drug in the first place.

Part of the problem lies in the fact that few people opt for the injectable version, given its high cost an the need for injections,” said Vinay Shetty of the Think Foundation, Mumbai. “Hardly 5,000 patients can afford to buy the injectable drug. Most people cannot afford the drug and the infusion pump. And compliance by children is difficult.” So most opt for the oral chelators that cost less but have side-effects.

India has an estimated one lakh patients with thalassaemia, a genetic disorder in which the blood cells cannot make sufficient amounts of the iron-containing pigment haeomoglobin. Haemoglobin gives blood its red colour and carries oxygen to various parts of the body. There are two groups of people with the defective gene responsible for the gene: thalassaemia minors, who carry only one copy of the defective gene, and thalassaemia majors, who carry two copies.

Of thalassaemia minors, there are 40 million in India alone, according to the Think Foundation, which works with the patients. Most are usually unaware that they are carrying the gene until they marry another thalassaemia minor person and make the unhappy discovery that their child has inherited two copies of the defective gene, and is destined to be a thalassaemia major for life. It is usually detected in the affected children between three and six months of age. From then on, they are dependent on lifelong blood transfusions.

However, blood transfusions result in an undesirable build up of iron, which accumulates in critical organs such as the heart, liver, pancreas and the spleen. Its build-up in the heart in particular can prove fatal and patients need to dispose off the excess iron regularly, through drugs called ‘iron chelators’ that pump the metal out.

Novartis’s Desferal – chemically, desferrioxamine (DFO) – is one such iron chelator that Kumar regularly takes as an injection. Desferal chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions. But the daily dose – 30-50 mg per kg body weight – needs to be injected slowly beneath the skin through an infusion pump over 8-10 hours, and is usually done at night.

Children require 10 vials each containing 500 mg of the drug every month. Adults require 100 vials each month. A set of 10 vials costs about Rs 1,700. The price has risen by almost five times since the 1980s. At that time, when Novartis first acquired the technology, a set of 10 vials cost Rs 30, recalled Kumar.

Oral tablets are available, too. An example is Deferipone, the first oral drug for iron chelation, known in India as Kelfer, the brand name under which it is made available by Cipla. “Kelfer has been known to work better with iron overload in the heart,” according to the Think Foundation. “However, some children show symptoms of nausea, vomiting, abdominal pains, diarrhoea and joint pains. Patients using this therapy must get blood tests and physical examination of joints done regularly.”

Another oral drug is ICL 670, initially introduced by Novartis in Europe as Exjade and later in India as Asunra. Cipla calls it Desirox. Although oral tablets are available, and are far cheaper, 50% of the patents reported side-effects such as nausea and joint pains, said Kumar. She also pointed out that generic versions of the injectable Desferal are available in the US, but not in India.

According to Muralidharan, the temporary shortage of Desferal “is not an isolated incident. Rather, it is the tip of the iceberg. The government should take initiative, for example, by granting import licenses, for the generic versions and also ensure that local pharma companies too make the injectable version.”

Shetty agreed to the suggestion: that the government should step in to ensure that at least all patients have access to the oral chelating drugs for thalassaemic patients. “The government should [also] look at the possibility of making oral chelators free for those who cannot afford them.”

Other crucial issues in the government’s regulatory blindspot are the ability of blood banks to cater to the transfusion needs of children; whether all children who have the disease are put on oral chelators at least even if their parents cannot afford them; and if a system is in place for regularly monitoring the heart, liver and spleen for early detection of any signs of iron accumulation.

In May, 2016, Kumar’s CHET submitted a draft policy on rare diseases to the director of India’s national health mission on the occasion of Rare Disease Day. India has an estimated 70 million people suffering from rare diseases, she says. But whether the government intends to act on the recommendations of the draft policy needs to be seen.

According to Kumar, there are over 7,000 rare diseases globally. The most prevalent in India are the  genetic defects that result in a defective haemoglobin molecule, or hemoglobinopathies, such as thalassaemia and haemophilia. Others include rare cancers, muscular dystrophy, auto immune diseases, and lysosomal storage disorders, a group of about 50 genetic disorders that leads to defective functioning of lysosomes and the accumulation of cellular waste products in them.

The draft policy draws the government’s attention to the fact that neither the national nor state health policies make any reference to rare genetic disorders despite the fact that the country has 70 million people afflicted with them. The draft recommends that India’s health policy should include a section on public health policy for rare disorders, to ensure access to affordable medicines and multi-disciplinary care for these patients. India’s national drug act should also, similarly, provide incentives to domestic pharmaceutical companies for producing ‘orphan’ drugs’.

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