Orphan Drug

An orphan drug is a pharmaceutical agent developed specifically to treat rare diseases or conditions, known as orphan diseases, which affect only a small percentage of the population. Because such diseases occur infrequently, the potential market for these drugs is limited, making their development commercially unattractive for pharmaceutical companies without government incentives. Orphan drugs play a vital role in addressing the medical needs of patients suffering from life-threatening or chronically debilitating rare disorders that would otherwise remain untreated.

Definition and Concept

The term orphan drug originates from the idea that these drugs are “orphans” of the pharmaceutical industry — neglected because they offer little financial return due to their small patient base.
A rare disease, as defined by various regulatory agencies, is a condition that affects a very small fraction of the total population:

• United States: Affects fewer than 200,000 people nationwide.
• European Union: Affects no more than 5 in 10,000 people.
• Japan: Affects fewer than 50,000 people.
• India: The National Policy for Rare Diseases (2021) classifies rare diseases based on prevalence, often below 1 in 10,000 individuals.

Drugs developed to diagnose, prevent, or treat such diseases are designated as orphan drugs and receive special regulatory and financial support from governments.

Background and Historical Development

Before the late twentieth century, patients with rare diseases were often neglected by both healthcare systems and pharmaceutical industries, mainly because of high development costs and low economic returns.
To address this gap, several countries introduced orphan drug legislations:

• United States Orphan Drug Act (1983): The first and most influential law promoting orphan drug development.
• European Union Regulation (2000): Established incentives and a framework for orphan drug designation within the EU.
• Japan (1993) and Australia (1997): Introduced similar legislation to stimulate research in rare diseases.

These policies encouraged pharmaceutical innovation through financial incentives, market exclusivity, and regulatory assistance, dramatically increasing the number of orphan drugs approved globally.

Characteristics of Orphan Drugs

1. Target Specificity:
   • Designed for rare diseases that often have genetic origins, such as cystic fibrosis, Gaucher’s disease, or Duchenne muscular dystrophy.
2. Small Market Size:
   • Intended for patient populations too small to make commercial success viable without incentives.
3. High Research Costs:
   • Research and clinical trials are expensive due to limited data and difficulties in patient recruitment.
4. High Price:
   • Orphan drugs often command high market prices to recover research and development costs.
5. Scientific Innovation:
   • Many involve biotechnology, gene therapy, or precision medicine techniques.

Examples of Orphan Drugs and Diseases

Some notable examples of orphan drugs include:

These drugs, though targeting small patient groups, have revolutionised treatment outcomes for individuals suffering from previously untreatable or fatal disorders.

Incentives for Orphan Drug Development

To promote research and innovation in rare disease therapeutics, governments and regulatory authorities offer several incentives to pharmaceutical companies:

1. Market Exclusivity:
   • Exclusive marketing rights for a fixed period (e.g., 7 years in the U.S., 10 years in the EU) even if patents expire earlier.
2. Tax Credits:
   • Tax relief on research and clinical trial expenses (up to 50% in the U.S. under the Orphan Drug Act).
3. Research Grants and Subsidies:
   • Public funding for preclinical and clinical studies.
4. Fee Waivers and Regulatory Support:
   • Reduced or waived regulatory submission fees and priority review processes.
5. Assistance in Clinical Trials:
   • Governmental and academic support for designing and recruiting patients for clinical trials.

These measures significantly reduce the financial risks of developing drugs for small patient populations.

Regulatory Frameworks and Agencies

Major international regulatory bodies overseeing orphan drug development include:

• U.S. Food and Drug Administration (FDA):
  • Administers the Office of Orphan Products Development (OOPD).
  • Grants “Orphan Drug Designation” under the 1983 Orphan Drug Act.
• European Medicines Agency (EMA):
  • Oversees the Committee for Orphan Medicinal Products (COMP).
  • Provides incentives and centralised authorisation for orphan medicines across the EU.
• Japan’s Ministry of Health, Labour and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA):
  • Manage Japan’s orphan designation process.
• India:
  • The Central Drugs Standard Control Organisation (CDSCO), under the Ministry of Health and Family Welfare, works alongside the Indian Council of Medical Research (ICMR) to promote rare disease research.
  • India’s National Policy for Rare Diseases (2021) provides partial funding for rare disease treatment and encourages local orphan drug production.

Challenges in Orphan Drug Development

Despite incentives, the development and accessibility of orphan drugs face several obstacles:

1. High Cost and Pricing:
   • Treatment costs can exceed several lakhs or even crores of rupees per year, limiting patient affordability.
2. Limited Clinical Data:
   • Small patient populations make it difficult to conduct statistically significant clinical trials.
3. Inequitable Access:
   • Patients in developing countries, including India, often lack access due to high costs, limited distribution, or absence of government reimbursement policies.
4. Ethical and Patent Issues:
   • Debate exists over granting long-term market exclusivity for drugs developed with public funding.
5. Regulatory Delays:
   • Differences in national regulations can slow down global approvals and availability.

Global Impact and Achievements

Since the introduction of orphan drug legislation, there has been a dramatic increase in innovation:

• Over 1,000 orphan drugs have received approval globally.
• The number of known treatable rare diseases has risen significantly.
• Advances in genomics and personalised medicine have improved understanding and treatment of rare disorders.

The orphan drug framework has also encouraged public–private partnerships, academic research collaborations, and patient advocacy movements, which continue to shape healthcare policies for rare disease patients.

Orphan Drugs in India

India’s engagement with orphan drugs is still developing:

• The National Policy for Rare Diseases (2021) aims to create a comprehensive strategy for rare disease diagnosis, treatment, and funding.
• The New Drugs and Clinical Trials Rules (2019) include provisions for waiver of clinical trials for orphan drugs already approved abroad.
• Financial Assistance: The government provides one-time financial support of up to ₹20 lakh per patient for certain rare diseases.
• Local Manufacturing: Indian pharmaceutical companies are encouraged to develop affordable biosimilars and gene therapies for rare disorders.

Despite these efforts, accessibility remains a challenge due to limited awareness, diagnostic infrastructure, and affordability.

Ethical and Social Dimensions

The orphan drug debate raises important ethical considerations:

• Equity vs. Profitability: Should rare disease patients be denied treatment because of limited market potential?
• Fair Pricing: How to balance company incentives with patient access and affordability?
• Global Justice: Ensuring equitable access in developing nations where healthcare resources are limited.