US $ 375,000 per year, US $ 365,000 per year, US $ 200,000 per year- these are costs of medicines per year per patient
for some genetic diseases. And these treatments need to be continued lifelong. Many of us cannot even imagine these
costs. It is like a mirage - the treatment is available but out of reach of many. Till date most treatments were affordable at
least for rich patients, but these newer costly therapies seem to be beyond the reach of rich families as well. These diseases
include Gaucher disease for which the deficient enzyme became available for treatment in 1991 as a prescription drug. The
successful strategy to target the enzyme to its intracellular location of action was applied to many other
lysosomal storage disorders like Hurler disease, Hunter disease, Maroteaux Lamy syndrome, all of which are
types of mucopolysaccharidoses and to Pompe disease which is a glycogen storage disease. The results are
miraculous. The facial coarsening, skin thickening, joint contractures and organomegaly improve as the
intracellular deposited material gets mobilized and broken down. The appearance of these MPS patients, once
described as ‘Gargoylism’, melts to normal over a period of months to years. Children with Pompe disease, if
started on enzyme replacement therapy during the neonatal period, attain normal milestones and do not
develop cardiac dysfunction. Of course the treatment needs to be continued lifelong. One more disease
which needs mention is Fabry disease, a disease with nonspecific symptoms and a cause of stroke or cardiac
dysfunction in young adults. It is also responsible for 1% of cases with chronic renal failure. Due to non specific
neuralgic pain without signs and inadequate awareness about the disease, the duration between onset of
symptoms and diagnosis, if it happens, is usually more than a decade. Now as the enzyme replacement
therapy (ERT) is available, early diagnosis is important. The timely initiation of treatment not only improves
the quality of life by reducing pain but also reduces the risk of damage to the heart and kidneys and of
stroke.
These enzyme replacement therapies are major milestones in medicine and in the treatment of genetic disorders. The
minds where the ideas were generated, beautiful and technologically innovative experiments in laboratories and on animal
models and double blind clinical trials confirming the efficacy of the drugs, cost a fortune. No doubt the cost will
have to be recovered when the drug is marketed. But the costs are exorbitant as described by treating
doctors in the US. Forbes has listed these drugs as one of the ten costliest drugs. Another such drug is
Ivacaftor, approved for cystic fibrosis cases with a specific mutation. This drug is one of the fastest drugs to
reach the market from its inception. The cost is US $ 311,000 per patient per year. Monoclonal antibody
for the treatment of paroxysmal nocturnal hemoglobinuria is costing US $ 409,500 per patient per year.
These costs are much more as compared to costly drugs like Zyprexa for schizophrenia (US $ 7,000) and
Avastin for cancer (US $ 50,000). Though the cost may be justified as the cost of innovation, who pays for it?
Even in developed countries, the rich patients also will not be able to pay from their pockets. It should
be remembered that many patient support groups like the Cystic Fibrosis Foundation and the Duchenne
Muscular Dystrophy Foundation have been supporting research in the development of therapeutics for these
disorders.
The rarity of these disorders contributes to the high costs of these drugs. The limited market for each of these drugs
makes them extremely costly. Most of these diseases have a prevalence of 1 per 40,000 or 1 lakh. Cystic fibrosis is
relatively common as compared to lysosomal storage disorders. There are about 30,000 people with cystic fibrosis in USA.
Out of them only 4-5% have the mutation G551D mutation and only these individuals will be benefited by Ivacaftor. For
such rare and neglected diseases, there is a concept of rare or orphan diseases, words which are used interchangeably.
There are about 5000 to 7000 rare diseases and 80% of them are genetic. For about 400 of them the treatment is available.
United States has the Rare Diseases Act of 2002 which defines rare disease as any disease or condition that affects
less than 200,000 people in the United States, i.e. about 1 in 1,500 people. This definition is essentially
like that of the Orphan Drug Act of 1983, a federal law that was written to encourage research into rare
diseases for possible cures. In Japan, the legal definition of a rare disease is one that affects fewer than
50,000 patients in Japan, or about 1 in 2,500 people. The European Commission on Public Health defines
rare diseases as “life-threatening or chronically debilitating diseases which are of such low prevalence that
special combined efforts are needed to address them.” They have excluded rare diseases without significant
mortality or morbidity. The European Organization for Rare Diseases (EURORDIS), the NIH’s Office of Rare
Diseases Research (ORDR), the National Organization for Rare Disorders and the Canadian Organization
for Rare Disorders (CORD) are organizations working for rare and orphan diseases. India does not have
any such separate approach to rare or genetic diseases or public programs for treatment or prevention of
them.
Though individually rare, given the large population of India, the absolute numbers of many of these diseases will be
quite large. The presence of high degree of consanguinity in some populations makes one feel that the numbers may be
higher than expected. As the new treatments are becoming available for rare diseases and the mortality due to infectious
and malnutrition-related diseases is decreasing, it is high time that the medical policy makers look at these diseases with
priority or at least do not neglect them. The beginning has been made. In many states the government has taken up the
responsibility of providing anti-hemophilic factors free of cost to the patients. This is mainly due to the efforts of the long
standing and active Hemophilia Federation of India. In some states the decision came through the court of
law. Though anti-hemophilic factors for home therapy has not been made available to the patients, serious
life-threatening bleeding episodes of many patients are being managed satisfactorily and elective and emergency
surgeries are being done, when needed. Some state governments have made iron chelation therapy free
for patients with beta thalassemia. All these efforts reflect the initiative taken by active patient support
groups.
It is painful for parents and doctors to see a patient suffering or dying of a treatable disorder. This is
still a reality in India as government health care is not satisfactory and state-of-the-art treatments though
available in India are accessible many a times to only people of high socioeconomic strata. As the country’s
governance improves and India marches towards the status of a developed country, the optimal health care
facilities for common and rare diseases need to be made available for one and all. The main issue of exorbitant
prices of these new drugs will continue to prevent access to these newer treatments for Indian patients,
rich and poor alike. The drug companies need to think about it. Their golden research needs to reach all
patients worldwide. This will not be possible till the prices are reduced drastically. The economics of drug
development, profits targeted, etc. are different in this new era of personalized medicine where there is a
separate drug for each mutation and there will be new medicine for each cancer genome. These need to be
looked at in a global perspective. From our side India needs to look at the issue from multiple perspectives.
Encouraging basic research and drug development is a necessity of the present time. Technology and scientists are
available in India to tap the research funding. The second is working with drug companies for pricing and also
organizing a very good government health care system with a three tier referral system. This will help us to
get area-wise data of patients of various disorders needing lifelong treatment. Electronic health records, if
implemented for all, will make such data collection easy. The Hemophilia Federation and hemophilia centers, for
instance, have data of patients registered with them, though many cases still remain undiagnosed and die
undiagnosed in the population. The data and facts about hemophilia patients helped the policy makers in
calculating the budget and in effectively planning the hemophilia management program. Collecting data
about population based prevalence is difficult or still next to impossible in India. But we doctors, especially
geneticists working for these rare disorders, can maintain a registry of these patients, which will go a long way
in carrying out research and establishing patient care facilities for these individuals suffering from rare
disorders.
The task ahead is difficult but the march towards the goal has already begun!
