Rare diseases: Millions in India suffer in silence

Sarthak Kamath is of a rare breed in more ways than one. On March 10 he became, as this year's Limca Book of Records will attest, the world's first duchenne muscular dystrophy (DMD) patient who's a qualified doctor.

That this genetic disorder is uncommon – DMD strikes 1 in 3,600 boys and seldom affects girls – is the bedrock for all hurdles he's contended with in his 24 years. What starts as proximal muscle weakness progresses to loss of movement until one is unable to stand. In advanced stages, DMD claims the muscles involved in breathing and circulation: namely, the lungs and heart. Modern medicine ensures that life expectancy can extend into the 50s, although the average is an estimated 25.

Diagnosed with DMD at age 12, Kamath has been wheelchair-bound for half his life.

"There's no cure. Some drugs developed for DMD were disapproved by the US Food and Drug Administration (FDA) for having disastrous side effects like kidney and liver failure," says Kamath over the phone from Bangalore, where he interns with MS Ramaiah Medical College.

For now, DMD treatment is multi-disciplinary: orthopaedic and respiratory devices, physical therapy to maintain muscle function and corticosteroids to curb symptom flare-ups. "A drug called Ataluren is in development, but it won't be accessible to all patients even if it passes regulatory tests because of the cost."

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Enzyme replacement therapy (ERT) drug Myozyme sets back Prasanna and Sharada Shirol by Rs1.3 crore every year. Their 16-year-old daughter Nidhi was the first Indian to be diagnosed with Pompe disease, a genetic disorder in the category of lysosomal storage diseases (LSD). Pompe has an incidence of 1 in 40,000 in the US, but official data for the number of patients in India – leave alone prevalence – does not exist.

"By the time she was a toddler, she couldn't stand on her own. It took seven years to get a definitive diagnosis," reveals Prasanna Shirol, founder-member of Organization of Rare Diseases India (ORDI).

Without timely detection, infantile onset Pompe disease claims life within 18 months of birth. Symptoms in adult or late onset Pompe include muscular degeneration, respiratory problems and scoliosis (especially during puberty). The root cause: absence of the enzyme alpha-glucosidae, which converts glycogen (complex carbohydrate) to glucose (simple sugar).

Myozyme is the tip of the expenditure pyramid. Hospital costs peaked when Nidhi was in the ICU for 45 days due to pneumonia. Then there was the onset of scoliosis, for which Rs29 lakh was spent on surgery. Another Rs15 lakh went into immunosuppression therapy after Nidhi's body developed a resistance to Myozyme. Costs of assistive devices – ventilators, traction machines, wheelchairs (which need to be changed every year) and a UPS – run upwards of Rs20 lakh. And there's ERT every fortnight.

"This isn't our story alone," underlines Shirol. "It's the story of all rare disease patients."

No country for the 'orphaned'

To say drug prices for rare or orphan diseases are steep is putting it mildly. Myozyme costs $531.20 or about Rs35,000 per 50mg vial, but Soliris is touted the world's most expensive drug. Prescribed for paroxysmal nocturnal hemoglobinuria (destruction of red blood cells by the immune system), it sets patients back by $700,000 (Rs4.6 crore) annually. But exorbitant excise and customs duties in India mean patients here will pay more.

There are only 500 therapies for 7,000 identified orphan diseases. And while the definition of 'rare disease' differs from country to country (see box), ORDI suggests a prevalence rate of 1 in 5,000. As per Indian Society for Clinical Research (ISCR), an estimated 70 million Indians – of which 50 per cent are children – suffer from rare diseases.

"Most Indian biotech companies feel there's no market because this 70 million spans thousands of diseases. Some have an incidence of 1 in 2,000; others, 1 in a million. Rarity is relative. But orphan diseases need lifelong therapies, and that should be an opportunity for them," says Dr. Meenakshi Bhat, clinical geneticist at the Centre of Human Genetics, Bangalore.

When asked if convincing biotech firms has been a struggle, Bhat, who's consulted over 15,000 patients – most of them below or just above the poverty line – laughs: "The simple answer is yes."

Orphan drug costs and 'market scepticism' aren't the only pitfalls. Many in the general medical community lack awareness about orphan diseases. Patients in rural and semi-urban India run from pillar to post because most prenatal screening and genetic counselling centres are in urban areas. And unlike the EU and the US, India has no orphan drug act. Rare diseases don't figure in central or state health policies, which focus on malnutrition, cholera, tuberculosis, etc.

"Selling the idea of making orphan drugs more accessible to those affected is a non-starter. Because the government believes it can better tackle common diseases within proposed health budgets," she says.

Lack of attention translates into absence of data. With no official numbers to present, pharmaceutical companies remain unconvinced about research and development (R&D) for treatment possibilities.

"If someone asks me 'How many patients of x disease are there, I have no answer. The only numbers I have are of those who come to my hospital. Markets for generic drugs can't be identified without national or state-wise data," stresses Bhat.

Relative history

In 2012, Dr Jayesh Sheth and his team at Ahmedabad's Institute of Human Genetics identified the first novel mutation of the fatal Tay-Sachs disease. One of the finds in this study was that Tay-Sachs has a higher prevalence in specific communities in Saurashtra – such as the Parmars. He also found, in Belgaum, that Batten disease, a deadly neuro-degenerative disorder, affected 72 per cent of child patients born to consanguineous (second cousins or closer) parents.

Sheth's years of research lead him to conclude that consanguinity is a risk factor for numerous rare, genetic diseases. "Since such marriages are encouraged in most communities, particularly in south and parts of western India, we have to take this seriously. The government should not only allocate funds and offer incentives for R&D, but sanction – not stall – approved projects," he says.

Of the abled, for the abled

The intersection of rare disease and a disabled-unfriendly India is perhaps the most compounding hurdle. Shilpi Bhattacharya, diagnosed with GNE myopathy, spells this out by not only pointing to inaccessible public transport and infrastructure, but also to lack of quality assistive devices such as ankle-foot orthotics (AFOs). "Patients have to buy them from abroad at expensive rates or approach local makers who don't understand needs of rare disease patients. The Indian government must encourage manufacturers to innovate in the making of AFOs so that a better variety of products are available at lower prices," says the member of World Without GNE Myopathy (India).

It's a view echoed by Sarthak Kamath, whose school treated him as a burden rather than responsibility by 'asking him to leave'. "I switched to a better institution but was without a school for six months. It was the first time I experienced depression in my life," he shares.

Well aware of such obstacles, Prasanna Shirol is working on Inclusive in India, a crowdsourced app that will map all disabled-friendly places in India, from toilets to hotels.

But the focus remains on a national or state-level rare disease policy. While Shilpi Bhattacharya is mobilising scientific and medical communities, ORDI, the Centre for Human Genetics and the Indira Gandhi Child Health Institute recently submitted a draft rare disease policy to the Karnataka state health department. And in an interim order in June 2015, the Karnataka High Court also ordered the state government to cover the treatment of 34 LSD patients.

"The final hearing is this week. Here's hoping," concludes Dr Bhat.

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What constitutes a rare disease?

Although there's no universal definition of a rare disease, the WHO has set the base prevalence rate at 1 in 2,000 people. While the US defines an orphan disorder as one that affects less than 200,000 people nationwide, in China, this changes to 1 in 500,000 people (or neonatal morbidity of less than 1 in 10,000).