By: Diya Gopalan

Most people haven’t heard of orphan diseases. That is because the term “orphan disease” refers either to a condition that only impacts a small number of individuals or as one that has been neglected by physicians. No universal definition or criteria currently exists. For example, in the United States, an orphan disease is recognized as one that affects fewer than 200,000 people, while in Europe, this statistic is 5 in 10,000 (roughly 246,000 people).[1] Globally, this translates to only 6% to 8% of the population [2].

Although orphan diseases only impact a relatively small proportion of individuals, they can have profound implications on patients, their families, and society at large. These diseases—which are usually chronic and progressive—pose immense challenges to both public health as well as the pharmaceutical industry. Many patients and doctors are waiting on strategies for efficient diagnoses and effective treatment options for this specific subsets of diseases.

A girl standing out in a crowd of people. Photo credits: Justice Amoh

The US coined the term “orphan” disease as a result of Congress’s Orphan Drug Act of 1983, which was initiated to incentivize drug companies to develop treatments for rare diseases. Drugs were given an orphan designation when used to treat diseases so rare that the cost of development would not be covered without financial incentives.[3] In a similar strategy, the European Union introduced its Regulatory Framework (141/2000) on orphan medicinal products in 1999 to grant orphan medicines market exclusivity. Since the execution of the Orphan Drug Act over 30 years ago, more than 340 treatments for orphan diseases were approved by the US Food and Drug Administration (FDA). In the EU, 133 medicinal products have been approved by the European Medicines Agency (EMA) to treat 122 rare conditions.[4]

Today, the National Institutes of Health (NIH) recognizes nearly 7000 orphan diseases, which impact up to 30 million Americans and Europeans. This list includes cystic fibrosis, amyotrophic lateral sclerosis (otherwise known as Lou Gehrig’s disease), as well as Tourette syndrome. The number of new rare diseases is accelerating quickly, most of which arise from genetic factors (80% of orphan diseases are caused by DNA mutations) with others attributed to extraneous environmental conditions.[5]

The visibility and recognition of orphan diseases remain a considerable challenge on a global scale. Limitations in the research of such conditions are primarily due to how relatively few patients are impacted, which causes a lack of standardized and available data. As a result, only a handful of physicians are familiar with possible diagnosis and treatment options. This lack of widespread knowledge often leads to undetected, delayed, or inaccurate diagnoses even when approved and effective therapies are available. These delays prolong disease processes and prompting greater risk of premature death for severe conditions.[6]

Given the unfamiliarity of orphan diseases, pharmaceutical companies often struggle with the task of developing unique, innovative therapies for patients with such uncommon forms of disease. Challenges exist from the beginning to end of an orphan drug’s lifecycle, especially during the research and development stage as well as clinical trial phases.[6] For instance, the diagnostic criteria for orphan diseases are constantly changing, creating difficulty in establishing true prevalence for clinical development and trial recruitment.[2]

The relatively low incidences of orphan diseases in individual countries calls for international cooperation on clinical trials to more strongly advance new therapies. In addition, foreseeable regulatory barriers as well as a potentially elevated cost and risk of manufacturing are obstacles in orphan drug development.[6] Overall awareness and engagement across the patient-, provider-, and policy-levels further requires substantial investment on behalf of pharmaceutical companies during their post-marketing efforts for orphan drugs.


Liquid pipetted into small plastic tubes. Photo credits: Louis Reed

The regulatory incentives provided to pharmaceutical companies have fueled considerable growth in the orphan drug industry. The US has even witnessed a discernible shift in drug spending from high-volume, low-cost drugs to precision drugs that generate greater value in patient outcomes. The International Rare Diseases Research Consortium (IRDiRC) has particularly been instrumental in raising public awareness about orphan diseases and facilitating various initiatives to improve collaboration between researchers and patients to better advance research. In fact, the Consortium’s goal of instituting 200 new therapies for orphan diseases by 2020 was achieved 3 years in advance, while its goal to diagnose most rare diseases by 2020 is very close to being attained.[7]

However, stricter regulations and invariably rising costs continue to discourage pharmaceutical players from pursuing research and developing orphan drugs. In 2016, only 34 new indications were approved, implying a stagnating orphan drug approval process.[7] The fact that orphan diseases do not capture a large enough market also remains a key reason as to why companies are reluctant to invest in the area. Nearly 50% of individuals with a suspected orphan disease are undiagnosed and individuals who receive a diagnosis wait an average of 5-6 years for the diagnosis. Moreover, 94% of rare diseases still currently lack an approved treatments.[7] It is imperative that more attention is drawn to this important public health issue in years to come. Collective engagement in research to advance diagnoses and treatment options for patients will help enable this.



  1. Aronson, J. (2006). Rare diseases and orphan drugs. British Journal Of Clinical Pharmacology, 61(3), 243-245. doi: 10.1111/j.1365-2125.2006.02617.x
  2. Auvin, S., Irwin, J., Abi-Aad, P., & Battersby, A. (2018). The Problem of Rarity: Estimation of Prevalence in Rare Disease. Value In Health, 21(5), 501-507. doi: 10.1016/j.jval.2018.03.002
  3. Herder, M. (2017). What Is the Purpose of the Orphan Drug Act?. PLOS Medicine, 14(1), e1002191. doi: 10.1371/journal.pmed.1002191
  4. Giannuzzi, V., Conte, R., Landi, A., Ottomano, S., Bonifazi, D., & Baiardi, P. et al. (2017). Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen. Orphanet Journal Of Rare Diseases, 12(1). doi: 10.1186/s13023-017-0617-1
  5. Institute of Medicine (US) Committee on Accelerating Rare Diseases Research and Orphan Product Development; Field MJ, Boat TF, editors. Rare Diseases and Orphan Products: Accelerating Research and Development. Washington (DC): National Academies Press (US); 2010. 2, Profile of Rare Diseases.
  6. Rare and Ultra-Rare Diseases. (2018). Alexion.
  7. Austin, C., Cutillo, C., Lau, L., Jonker, A., Rath, A., & Julkowska, D. et al. (2017). Future of Rare Diseases Research 2017-2027: An IRDiRC Perspective. Clinical And Translational Science, 11(1), 21-27. doi: 10.1111/cts.12500





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