What is an Orphan Drug?
Understanding Rare Diseases
The Role of Orphan Drug Legislation
Why are Orphan Drugs Important?
Challenges in Developing Orphan Drugs
Recent Advances and Success Stories
The Future of Orphan Drugs
In Summary
The 20th and 21st centuries have witnessed a profound revolution in medical science, significantly enhancing living standards and extending the life expectancy of billions worldwide. However, certain diseases and medical conditions continue to receive less funding and attention compared to others.
Patients with rare medical conditions and diseases are often part of a traditionally underserved population. However, “orphan drugs” provide hope by offering treatment options that improve their quality of life and potentially extend life expectancy.
Image Credit: unoL/Shutterstock.com
What is an Orphan Drug?
“Orphan” diseases affect small patient populations. In the US, to be considered an orphan disease, it must affect under 200,000 patients. Typically, funding for treatment can be difficult to come by, with only 600 “orphan” drugs approved for use by the US Food and Drug Administration (FDA).1
The term’s origin can be found in the 1960s when Dr Harry Shirkey wrote an article called “Therapeutic Orphans.” Changes in legislation and regulation in that decade led to some drugs being “orphaned” as they were no longer cost-effective for drug companies due to a lack of market demand. Thus, there has historically been little financial incentive for pharma companies to develop drugs to treat rare diseases.2
Market Report 2025: Pharmaceutical Manufacturing
Understanding Rare Diseases
Whilst a rare disease is defined as affecting under 200,000 patients in the US, the global patient population living with these types of disease is estimated at 3.5-5.9%. This is in the range of 263 to 446 million people worldwide.3
Rare diseases include well-known types of diseases such as Cystic Fibrosis, ALS, and hemophilia, as well as rarer types of cancers.
Metabolism disorders, autoimmune diseases, autoinflammatory syndromes, cerebrovascular disorders, degenerative diseases such as Duchenne muscular dystrophy, and Creutzfeldt-Jacob disease (a prion disease) all fall under the umbrella of rare diseases.
There are over 10,000 known medical diseases with a significant cumulative burden. Not only patients are affected, but family members and communities can feel the impact of these rare and hard-to-treat conditions.
5 Myths About Orphan Drugs and the Orphan Drug Act
The Role of Orphan Drug Legislation
As explained above, the rarer a disease is, the less financial incentive there is for pharma companies to research and develop a drug to treat it. However, whether there is any financial incentive or not, patients still suffer the effects of these diseases.
The role of legislation has been critical for the development of drugs for these diseases. It would be the drafting of legislation such as the Orphan Drug Act (1983) in the US and the EU Regulation on orphan medicinal products that would make it easier for orphan drugs to come to market.4,5
The Orphan Drug Act (1983) incentivizes the development of orphan drugs by providing tax incentives, research subsidies, and exclusive marketing rights for companies for 7 years once an orphan drug comes to market. Since the act was introduced, over 880 orphan drugs have been approved for use by the FDA.4 Similarly, in the EU, over 200 orphan drugs have been authorized due to legislation.
Why are Orphan Drugs Important?
As can be seen, orphan drugs have been historically critically underfunded, and in some cases, even today, they can face financial pressures that limit their release onto the market. However, at the foundation of orphan drug research can be found the patients themselves and their unmet medical needs.
The COVID-19 pandemic demonstrated the inequalities and disparities across different patient populations and demographics, and this has parallels in the rare disease sector.
The UN has now recognized the importance of addressing these disparities, promoting greater integration of rare and orphan diseases into policies.3 The goals of rare disease research and universal health coverage targets share a commonality.
Orphan drugs do not just improve the lives of those suffering from rare diseases, as mentioned previously in this article. Better funding and improved access to therapies also impact the families and communities of patients.
These drugs bring social and economic benefits; for example, relieving the symptoms of a rare disease can reduce care needs and burdens on family members.
Furthermore, orphan drugs drive advancements in precision medicine and biotechnology. Innovation in this area can have a positive impact on related biomedical fields.
Challenges in Developing Orphan Drugs
There are still several challenges with orphan drugs, although bringing them to market has been made easier by legislation.
High development costs, limited financial returns, difficulty in conducting trials due to small patient populations, and the high price of orphan drugs are all roadblocks to their market adoption.
High costs create access issues for patients and healthcare providers. Moreover, insurance companies may be less willing to cover the costs of orphan drugs due to the high costs and perceived lack of financial return associated with them.
Drug Delivery: An Overview
Recent Advances and Success Stories
Since the introduction of legislation such as the Orphan Drug Act, there have been several success stories in the orphan drug and rare disease sector.
Ivalfactor and Kalydeco are drugs that treat Cystic Fibrosis, a debilitating condition that affects nearly 200,000 people worldwide. Spinraza is an orphan drug used to treat spinal muscular atrophy.
Coagulation factor IX has been developed to prevent bleeding in hemophilia B patients. Rucaparib is a drug that was approved for ovarian cancer. Porphyria can be treated using Haem arginate.
Innovations such as targeted therapies and gene therapy are accelerating research into rare diseases and orphan drugs. Personalized medicine is having an impact on areas such as orphan drug designation and pricing strategies.6
The Future of Orphan Drugs
The need for orphan drugs and therapeutics options for traditionally underserved patient populations has driven legislation and cooperation between governments, pharma companies, and patient advocacy groups in recent years.
This is likely to continue over the coming years and will continue to impact health outcomes for millions of patients worldwide.
Furthermore, innovations in areas such as AI-powered drug discovery, machine learning, synthetic biology, and genomics are accelerating orphan drug development.
The emerging role of AI, for instance, is a pivotal moment in pharmaceutical research, improving the speed of drug target discovery exponentially. Novel molecules can be designed, and patient response markers can be better identified.
Synthetic biology can help target identification. Novel biopharmaceuticals can be designed using these innovations. This can only benefit the development of orphan drugs for rare disease treatment in the future.
In Summary
Millions of patients worldwide suffer from rare diseases such as Cystic Fibrosis, Duchenne muscular dystrophy, cancers, neurological disorders, and autoimmune diseases.
Orphan drugs offer hope to these historically underserved patient populations, but a lack of funding and research focus makes releasing them to market problematic.
However, legislation, innovation, and increasing collaboration between multiple stakeholders, including patient advocacy groups, have resulted in more orphan drugs being approved in recent years, improving patients' quality of life and health outcomes.
Further innovation and continued focus on advocacy for orphan drugs will be necessary to build on this global medical success story.
Referencing
- Chao, S (2024) What is an Orphan Drug? [online] drugs.com. Available at: https://www.drugs.com/medical-answers/orphan-drug-3562491/ (Accessed on 18 January 2025)
- Mikami, K (2019) Orphans in the Market: The History of Orphan Drug Policy Social History of Medicine 32:3 pp. 609-630 [online] Oxford Academic. Available at: https://academic.oup.com/shm/article/32/3/609/4663001 (Accessed on 18 January 2025)
- Claudia Ching Yan Chung et al. (2022) Rare disease emerging as a global public health priority Frontiers in Public Health 18:10 [online] National Library of Medicine. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9632971/ (Accessed on 18 January 2025)
- National Organization for Rare Disorders (2023) The Orphan Drug Act [online] NORD. Available at: https://rarediseases.org/wp-content/uploads/2023/11/NORD-ODA-Explainer.pdf (Accessed on 18 January 2025)
- European Commission (2025) Orphan medicinal products [online] Available at: https://health.ec.europa.eu/medicinal-products/orphan-medicinal-products_en (Accessed on 18 January 2025)
- Degtiar, I (2017) A review of international coverage and pricing strategies for personalized medicine and orphan drugs Health Policy 121: 12 pp. 1240-1248 [online] ScienceDirect. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0168851017302336 (Accessed on 18 January 2025)
Further Reading