The Concept of Orphan Drugs for Orphan Diseases is Orphan in India

Though the percentage of patients suffering from ‘Rare Diseases’ in India is reportedly higher than the  world average, unfortunately even today such cases get little help from our government.

According to experts, diseases manifesting patients representing maximum 6 to 8 percent of the world population are defined as ‘Rare Diseases’ and most of such diseases being ‘Orphaned’ by the global pharmaceutical industry, mainly because of commercial considerations, are termed as ‘Orphan Diseases’. Consequently when any drug is developed specifically to treat an ‘Orphan or a Rare Disease’ condition is called an ‘Orphan Drug’.

According to SanOrphan SA, Geneva, Switzerland, around 65 percent of rare diseases are serious and disabling. More interestingly, about 250 new rare diseases are discovered each year, corresponding to five new rare diseases per week.

However, without appropriate ecosystem being in place, developing a new drug (Orphan Drug) specifically to treat a very small number of patient populations suffering from any particular type of rare disease through highly cost intensive R&D initiatives, generating a low return on investments, has been extremely challenging for any pharmaceutical company.

The challenge and the need:

Public awareness drives for ‘Orphan Diseases’ first originated in the USA with the formation of a rare disease support group representing around 200,000 patients suffering from such ailments.

However, very limited market especially for those ‘Orphan Drugs’ , which are meant for the treatment of a single rare disease, has been discouraging the large pharmaceutical players to make major R&D investments for such molecules, as mentioned above.

In response to the public awareness campaigns and at the same time understanding the commercial imperatives of the pharmaceutical companies in developing “Orphan Drugs’, a path breaking legislation was formulated by the U.S government way back in 1983, known as ‘Orphan Drugs Act (ODA)’. The key purpose of ODA was to incentivize R&D initiatives for such drugs to treat around 25 million Americans suffering from ‘Orphan Diseases’.

Though similar legal and policy interventions are of utmost importance to allay the sufferings of millions of patients fighting rare diseases in India, precious little has been initiated in this direction by the government, thus far.

Orphan Drugs in the USA:

U.S Food and Drug Administration (US-FDA) provides orphan status to drugs and biologics which are defined as:

  • Those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S.
  • Or, those affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.

India perspective:

For the first time in India, to increase awareness for the rare diseases, Rare Diseases Day was observed in New Delhi on February 28, 2010. Subsequently 2nd and the 3rd ‘Rare Disease Days’ were observed in Chennai and Mumbai in 2011 and 2012, respectively.

About 6000 to 8000 rare diseases, mostly genetic in nature have been identified in India. It was initially estimated that over 31 million Indians are suffering from rare diseases in the country, many of these diseases still do not have any cure.

However, The Hindu in April 2012 reported, “Taking the lower limit of global prevalence estimate, populous nations like India and China should have more than 70 million rare disease cases each.”

Inaction in India:  

The report further highlights that enough awareness has still not been created in India to address this challenge, despite publication of several rare disease case reports in the peer reviewed journals and existence of a number of support groups, though with inadequate resources.

Use of ‘Social Media’ to increase awareness:

Even in the developed markets, leave aside India, it is still hard to get required health related information for individuals suffering from rare diseases. In many countries, finding no better alternatives, such patients decide to be virtual experts on the diseases they are suffering from, making full use of social media, like Facebook.

Interaction through social media often makes it easier for such patients not only to find each other, but also to share expertise and experience eventually to get proper medical care with affordable drugs.

‘Orphan Drugs Act’ must come with adequate incentives:

ODA, when enacted in India, should not be a half-hearted approach or be a zero-sum game for all. It should come with adequate financial and other incentives to create a sound business sense in this new ball game for the pharmaceutical players in India.

Just for example, the incentives of the ODA in the U.S include:

  • Funding towards investigation for “Orphan Disease’ treatment
  • Tax credit for Clinical Research
  • Waiver of fees for New Drug Application (NDA)
  • Offering more lucrative incentive than product patent (product patent requires the drug to be novel), as the orphan designation of the product by the US FDA and product approval by them are the only requirements for 7 year market exclusivity of an ‘Orphan Drug’ for the specified indication
  • Market exclusivity of ‘Orphan Drugs’ become effective from the date of regulatory approval, unlike product patent, product development time remains outside this period
  • The drugs, which are not eligible for product patent, may be eligible for market exclusivity as an ‘Orphan Drug’ by the US-FDA

Proof of the pudding is in the eating:

Thanks to this Act, currently around 230 ‘Orphan Drugs’ are available in the U.S for the treatment of around 11 million patients suffering from rare diseases. With the help of ‘Human Genome Project’ more orphan diseases are expected to be identified and newer drugs will be required to treat these rare ailments of human population.

‘Orphan Drugs Act’ encourages ‘Orphan Drugs’ development:

It is now a reasonably well accepted fact that ‘Orphan Drugs Act’ encourages ‘Orphan Drugs’ development.

In an article titled, “What the Orphan Drug Act has done lately for children with rare diseases: a 10-year analysis”, published by the National Center for Biotechnology Information (NCBI), U.S, National Library of Medicine, the authors articulated that in the U.S. 1138 orphan drugs were designated and 148 received marketing approval, of which 38 (26%) were for pediatric diseases, from 2000 to 2009. The percentage of approvals for pediatric products increased from 17.5 (10 of 57) in the first half of the decade, as compared to 30.8 (28 of 91) in the second half.

Based on the data the paper concluded that incentives provided in the ‘Orphan Drugs Act (ODA)’ of the United States of America, have led to increased availability of specific drugs for the treatment of ‘Rare Diseases’ in the country.

Others followed… but when will India…?

As stated above, 1983 signaled the importance of ‘Orphan Drugs’ with the ‘Orphan Drugs Act (ODA) in the U.S. A decade after, in 1993, Japan took similar initiative followed by Australia in 1999. Currently, Singapore, South Korea, Canada and New Zealand are also having their country specific ODAs.

Following similar footsteps, India should also encourage its domestic pharmaceutical industry to get engaged in research to discover drugs for rare diseases by putting an ‘Orphan Drugs Act’ in place, extending financial support, tax exemptions and regulatory concessions like smaller and shorter clinical trials, without further delay.

Every day millions of Indians will continue to suffer from ‘Orphan Diseases’ without affordable treatment, in the absence of an appropriate policy framework in the country for ‘Orphan Drugs’.

Another vindication of the argument:

It is worth repeating that an ODA with proper incentives has been the key motivating factor for the development of many drugs and treatment for a large number of rare diseases, since 1983.

Looking at the increasing number of approvals, it appears that CAGR of ‘Orphan Drugs’ will now be far greater than other drugs. Even in 2011 as many as 11 ‘Orphan Drugs’ have been approved by the US-FDA, as stated below:

Company Brand Name Generic Name Type of Approval Indication Month in 2011
Bristol-Myers Squibb YERVOY Ipilimumab New biologic licence application Metastatic Melanoma March
IPR Pharmaceuticals CAPRELSA Vandetanib New molecular entity Advance medullary thyroid cancer April
Bristol-Myers Squibb NULOJIX Belatacept New biologic licence application Prevent organ transplant rejection June
Seattle generics ADCETRIS Brentuximab vedotin New biologic licence application Hodgkin lymphoma and systemic anaplastic large cell lymphoma August
Roche ZELBORAF Vemurafenib New molecular entity Metastatic melanoma August
Shire FIRAZYR Icatibant acetate New molecular entity Hereditary angioedema August
Pfizer XALKORI Crizotinib New molecular entity Late stage lung cancer August
ApoPharma FERRIPROX Deferiprone New molecular entity Thalassemia October
Lundbeck ONFI Clobazam New molecular entity Seizures associated with Lennox-Gastaut syndrome October
Incite JAKAFI Ruxolitinib New molecular entity Myelofibrosis November
EUSA Pharma ERWINAZE Asparaginase Erwinia chrysanthemi New biologic licence application Acute lymphoblastic leukemia November

(Source: Ernst & Young, FDA and company website. 2012)

The above facts, once again, vindicate the argument that the ODA of the kind of the U.S, broadly speaking, is worth emulating by India with appropriate modifications as relevant to the country.

The global Market:

A new report from Thomson Reuters indicate that the global market for ‘Orphan Drugs’ was over US$50 billion in 2011.

It has also been reported that ‘Orphan Drugs’ contribute 6 percent of US$ 880 billion global pharmaceutical market with a CAGR of 25.8 percent as compared to 20.1 percent for ‘Non-Orphan Drugs’ during 2001 to 2010 period.

High price of ‘Orphan Drugs’ is an issue:

The most challenging part in the fight against ‘Orphan Diseases’ is access to an affordable treatment, especially to affordable ‘Orphan Drugs’.

For obvious reasons, the prices of ‘Orphan Drugs’ are usually very high, some even costs as high as US$ 400,000 annually and thus beyond affordability of many who are outside the purview of any drug price reimbursement scheme.

Most of such drugs are rarely available in India and there is no reasonably affordable ‘rupee’ price for these drugs. Indian patients suffering from rare diseases will currently have no other alternative but to import these drugs directly in US$ term, unless Indian policy makers wake-up some day and take appropriate measures in this important area.

Additional commercial opportunities could be available with appropriate ODA:

Thomson Reuters reported additional commercial opportunities with an appropriate ODA, which are as follows:

  • 15 percent of the ‘Orphan Drugs’ analyzed by them had subsequent launches for other rare illnesses.
  • 6 out of the top 10 ‘Orphan Drugs’ had more than one rare disease indication with an average peak sales of US$ 34.3 billion in overall sales potential against around US$ 8.1 billion of the same for drugs with single indication.
  • Time taken for Clinical Trials (CT) focused on orphan drugs is significantly shorter with a quicker review time than trials involving non-orphan drugs.


It is interesting to note that some of the ‘Orphan Diseases’ are now being diagnosed also in India. As the nation takes rapid strides in the medical science, more of such ‘Orphan Diseases’ are likely to be diagnosed in our country. Thus the moot question is how does India address this pressing issue with pro-active measures, now?

One of the ways to properly address this issue in India could well be to follow the model of our very own the Council of Scientific and Industrial Research (CSIR) for an ‘Open Source Drug Discovery’ (OSDD) program with global partnerships, wherever necessary.

Thus in my view, with an appropriate ODA in place, leveraging the knowledge of OSDD acquired by CSIR and framing a robust win-win Public Private Partnership (PPP) model to discover and commercialize the ‘Orphan Drugs’, India could well demonstrate that the concept of Orphan Drugs for Orphan Diseases is really not Orphan in India.

By: Tapan J Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

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