ORPHAN DRUGS

Ancy JoseBiotechnology Engineering2011-2015 BatchSCET,Kodakara

Neglected Diseases: Rare diseases and tropical diseases.

Any disease that affects a small percentage of the population.

About 250 new rare diseases are discovered each year.

Medical literatures describe about 7000 rare diseases ; in that 650 have received official designation as rare diseases (Europe)

The known rare diseases include : Autoimmune Diseases, Cancer

Types, Communication Disorders, Cutaneous Conditions, Endocrine Diseases, Eye Diseases And Disorders,

Genetic Disorders(80% ), Infectious Diseases, Intestinal Diseases, Neurological Disorders.

Orphan Diseases

Diseases that manifest in patient populations representing at the maximum 6–8% of the world population are defined as “rare diseases” or “orphan diseases”.

Any drug is developed to treat an ‘orphan or a rare disease’ condition is called an ‘Orphan Drug’.

The lack of economic feasibility leads to a lack of even preliminary research into these disorders.

These are not developed by the pharmaceutical industry for economic reasons but which respond to public health need.

Developing a orphan drug is extremely challenging for any pharmaceutical company because of :

High cost intensive R&D initiatives Availability of a low return on investments.

Orphan Drugs

Classification Of Orphan Drugs

Basis for the discovery of Orphan drugs:

Determination of the human genome sequence by the International Human Genome Project,

Advances in genomics and proteomics, and

A detailed understanding of cellular biochemical networks

The Orphan Drug Act (ODA) was passed on January 28, 1983.

USA was the first nation to propose a legal frame work to encourage development and availability of orphan drugs.

Following the same policy as the US, Singapore (1991), Japan (1993) and Europe (2000) passed laws with aim to promote research and development in the field of rare diseases .

A group of pharmacologists requested the Indian government to institute ODA at the conference held by the Indian Drug Manufacturing Association in November 2001, but nothing concrete has materialized so far.

Orphan Drugs Act

Incentives Of ODA.

Funding towards investigation for "orphan disease" treatment

Tax credit for clinical researchWaiver of fees for new drug applicationOffering more lucrative incentive than product

patent (product patent requires the drug to be novel), as the orphan designation of the product by the US Food and Drug Administration (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.

Recommendations from FDA staff to sponsors about nonclinical and clinical studies that would support approval of a drug for a rare disease.

Other special assistance, such as accelerated approval or fast track or priority review, may also be available for sponsors of orphan drugs.

Tax-incentives accelerate and support R & D for rare disease for the discovery and development of medicines, diagnostics, and vaccines for rare diseases, with a suitable level of pricing for the patients, families and health insurances

Since the introduction of ODA, nearly 1100 drugs and biological products have been designated as orphan products.

The FDA has approved over 231 of these for marketing, thereby facilitating treatment for an estimated 11 million patients in the USA.

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 ODA.

But India has still not inacted the Orphan Drug ACT

Impact Of ODA

Hyderabad based NATCO Pharma’s novel anti-cancer drug (NRC-AN-019) has received “Orphan Drug Designation” from the USFDA for three indications-

Glioma (brain tumor) Pancreatic cancer Chronic Myelogenous Leukemia.

Orphan Drugs In India

Troikaa pharmaceuticals Ahmedabad manufactures following orphan drug preparations:

Tachyban (adenosine injection)

Hemaprot (aprotinin injection)

Neopam (pralidoxime chloride injection)

Narcotan(naloxone hydrochloride injection)

Cyan sos

The Cipla’s Mumbai-headquartered firm is manufacturing the fixed dose combination drug of Artesunate and Mefloquine (ASMQ FDC) under a technology transfer agreement with Neglected Diseases initiative (DNDi).

The combination of AS and MQ is one of five Artemisinin Combination Therapies (ACTs)currently recommended by WHO for the treatment of uncomplicated P.falciparum malaria, and is the first-line treatment in a number of South East Asian countries.

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.

In 2014, Lysosomal Storage Disorders Support Society observed Rare Diseases Day in Bangalore, New Delhi, Mumbai, Chennai, Jaipur, & Kolkata

Indian Scenario

400 US FDA approved orphan drugs and about 80 EMA approved orphan drugs are available in India and world-wide.

Most of them are either not accessible to most patients in India or are unaffordable.

Still effective research is not widespread in india.ORDI aims to work between the Government of India

and the Pharma/Biotech/Diagnostic industry to enact an Orphan Drugs Act.

The National Institute of Pharmaceutical Education and Research is getting into research on ‘orphan drugs’ to solve the rare diseases problem in India

Examples….

High prices of “orphan drugs”Small patient populationDelay in diagnosis & Deficient diagnostic

systemsLimited treatment availabilityLack of knowledge & trainingDisease is poorly understood Lack of adequate expertise and review by

authoritiesLimited public awareness

Challenges In Orphan Drug Development