Understanding orphan drugs: what are they, how are they classified and what are their challenges in the Indian context Premium

Orphan drugs crucial for rare diseases, India faces challenges in development, affordability, and accessibility compared to other countries.

Orphan drugs, critical in treating rare diseases, have increasingly gained attention in India following the implementation of the National Policy for Rare Diseases (NPRD) in 2021. Despite this, India faces significant challenges in ensuring the development, affordability, and accessibility of orphan drugs, especially compared to other countries like the United States and the European Union. While global frameworks such as the Orphan Drug Act (ODA) of 1983 in the U.S. have successfully incentivised pharmaceutical companies to invest in these drugs, India is still in the early stages of establishing a robust system that can address the needs of its rare disease patients.

Orphan drugs are pharmaceutical agents developed specifically to treat rare (orphan) diseases. These diseases, though affecting only a small portion of the population, often lead to life-threatening or chronically debilitating conditions. Definitions of orphan drugs vary depending on the regulatory framework. In the U.S., a disease is considered rare if it affects fewer than 2,00,000 people, while in the European Union, a disease must affect fewer than 1 in 10,000 people to be considered rare. Although there is no formal prevalence-based definition in India, the NPRD of 2021 outlines a framework for diagnosing and treating rare diseases, with a low prevalence threshold expected. The lack of a clear definition complicates the identification of orphan drugs and the addressing of needs of patients affected by these conditions.

Orphan drugs are categorised based on the types of diseases they target and their regulatory status. Diseases such as genetic disorders, rare cancers, metabolic disorders, and autoimmune conditions frequently fall under the orphan disease category. Genetic disorders include conditions like cystic fibrosis and Duchenne muscular dystrophy, while rare cancers like neuroblastoma and gliomas also qualify for orphan drug development. Metabolic disorders, such as Gaucher’s disease and Fabry disease, and autoimmune diseases, like systemic sclerosis, also benefit from orphan drugs. Orphan drugs are further classified as approved by regulatory agencies like the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) or orphan drug candidates still undergoing clinical trials. These classifications are critical in determining the availability and potential efficacy of treatments for rare diseases.

Under India’s NPRD, rare diseases are classified into three categories to facilitate treatment approaches. Group 1 includes disorders that are curable through one-time interventions, such as Lysosomal Storage Disorders (LSDs) requiring Hematopoietic Stem Cell Transplantation (HSCT). Group 2 encompasses diseases that need long-term or lifelong management but have relatively lower treatment costs, such as Phenylketonuria (PKU) and Maple Syrup Urine Disease (MSUD). Group 3 covers conditions like Gaucher Disease and Pompe Disease, where treatment is available but complicated by high costs and the necessity for lifelong care.

For a drug to receive orphan drug designation, it must meet certain criteria that vary across countries. Typically, the disease in question must have a low prevalence. Additionally, the condition must lack approved treatments, or the orphan drug must provide significant benefits over current treatment options. Developers of orphan drugs must also provide scientific evidence that the drug has the potential to treat or alleviate the condition. This evidence can be presented at any stage of drug development, from preclinical research to late-phase clinical trials. Once designated, orphan drugs receive several incentives to encourage their development, including market exclusivity, tax credits for research and development (R&D) expenses, and fee waivers for regulatory applications.

Although orphan drug development has been incentivised globally, significant challenges remain, particularly in countries like India. The high cost of research and development is a major barrier, as orphan drugs often target small patient populations, making it difficult for pharmaceutical companies to justify the financial risk. Clinical trials for orphan drugs also face hurdles due to the limited number of patients available, prolonging development timelines. Pricing and accessibility are additional challenges, as the high costs of orphan drugs often make them unaffordable for patients in low- and middle-income countries like India. For instance, enzyme replacement therapies (ERTs) for diseases like Gaucher’s disease can cost several crores annually, placing them out of reach for most Indian patients.

India faces unique challenges in the development and accessibility of orphan drugs despite efforts like the NPRD. The country lacks a formal definition and comprehensive data on the prevalence of rare diseases, which hampers drug development efforts. Without a centralised national registry for rare diseases, it is difficult to estimate the true burden of these conditions, limiting pharmaceutical investment in orphan drug research.