Rare Disease Research

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Rare Disease and Orphan Disease - Defining the Terms

The term rare disease does not have a universal definition in Asia, Africa, South America, or the Middle East. This term is defined by individual countries that impose their own quantitative thresholds on disease prevalence. Many countries in these regions have not adopted a formal definition for a rare disease, and in the developing world misreporting of rare disease statistics is common. The term orphan disease is typically used as a synonym for rare disease in these regions, but may also refer to diseases which are common but not economically desirable to treat.


  • The definitions of the terms rare disease and orphan disease differ by country in Asia, Africa, South America, and the Middle East, if defined at all. Orphan diseases may also include more common diseases that are unprofitable to treat, but the terms are frequently used as synonyms.
  • In Asia, Taiwan defines a rare disease as one that occurs in fewer than 1 in every 10,000 people; 220 such diseases have been identified. China defines a rare disease as occurring in fewer than 1 in 500,000 people in the general population and fewer than 1 in 10,000 newborns; 121 such conditions have been identified. Japan defines a rare disease as occurring in less than 1 in every 50,000 people. South Korea and Singapore define a rare disease as one that occurs in fewer than 1 in 20,000 people.
  • In South America, Argentina, Chile, and Mexico have adopted the EU definition of fewer than 1 in every 2,000 people. Brazil defines a rare disease as one affecting less than 65 in every 100,000 people. Colombia defined a rare disease in 2016 as a disease occurring in less than 1 in every 5,000 people.
  • In Saudi Arabia, a rare disease is defined by the Ministry of Health as "conditions that affect populations not exceeding 5 in 10,000 individuals." Turkey's Ministry of Health defines a rare disease as a disease affecting less than 1 in 100,000 persons. Israel defines a rare disease as a condition that affects 1 in 1,000 people.
  • There is no rare disease registry in Africa. Many individual African countries, such as Ghana, do not have a definition of rare disease at the national level.
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Grouping of Rare Diseases

Grouping of rare diseases varies according to the motivation — whether the grouping is taking place in order to track disease rates, care, or to facilitate research or funding. The most common way to group rare diseases seems to be based on body systems.

Types and categories of rare diseases — US

  • In the U.S., certain rare diseases are tracked after diagnosis, based on category, and these include infectious diseases, birth defects, and cancers. Other rare diseases are not tracked.
  • The National Organization for Rare Diseases has a database of rare diseases, available for patients, cares, and doctors. The diseases are organized alphabetically and are not categorized into any type of groups.
  • The Genetic and Rare Disease Information Center groups rare diseases by body systems, and their information specialists also assign diseases into categories. There are 32 categories in total, and they include new born screening, mouth diseases, nervous system diseases, fungal infections, female reproductive diseases, blood diseases, and more.

Types and categories of rare diseases — Europe

  • Existing rare disease networks in Europe also seem to be grouped around body systems, and they include rare cardiac diseases, rare hereditary metabolic disorders, hematological diseases, cancers, hepatic diseases, skin diseases, and more. Examples of some of the specific networks formed within these groupings include Rare Dysmorphic Syndromes, Rare Bleeding Disorders, Congenital Heart Defects, European Network for Rare and Congenital Anaemias, Information Network on Rare Cancers, and more.
  • While the above model seems to be the most common way to group rare diseases (and diseases in general), there are several possible models such as: "the alignment of diseases by clinical area (e.g. Neurology, Neuromuscular, Psychiatry, Skin, Kidney, etc.), by clinical group (e.g. Genetic Disorders, Metabolic Disorders, Epilepsy, Oncology), clinical intervention area (e.g. Transplantation, Gene Therapy, Radiotherapy), shared molecular aetiology [11] (e.g. Underlying disease mechanism or pathway such as fibrosis or inflammation) or mixed models."
  • However, most European research and development rare disease networks are grouped by clinical area or clinical grouping (e.g. rare anaemias, neuromuscular diseases, metabolic diseases, rare epilepsies, etc.).
  • Within clinical groupings there are different systems for grouping diseases: the Classical Medical Ontology; the Orphanet classification; the EURORDIS preliminary proposal for grouping of rare diseases; the French filières; and the UK Research Model as established by the NIHR Translational Research Collaboration on RD.
  • Orphanet suggests 31 rare disease categories. These include cardiac diseases, rare swallowing disorders, inborn errors of metabolism, respiratory diseases, and more. Click on the Classifications of Rare Diseases button on this link for a pop up which lists all of the categories, and for each category, notes their schema and definitions.
  • EURORDIS groups rare diseases into categories like undiagnosed conditions, cardio-vascular, endocrinal, kidney, and women, neonatal, and children, for a total of 19 groups.
  • The UK has 14 groups, which are quite broad, and include cancer, eye disease, skin, and renal diseases.

How rare diseases are grouped together - methodologies and criteria

  • In Europe, the creation of European Reference Networks in order to guarantee equity in access to health care has been a driving force behind investigating the thematic grouping of rare diseases. These networks can help overcome the specificities of rare diseases: scarcity of patients, resources and expertise. Hence, the methodology for grouping rare diseases was based on how each disease would benefit from networking.
  • Specifically, these groupings and networks had to meet the following criteria, by facilitating: "easier adoption and spread of innovations in medical science and health technologies; facilitation of medical training; faster dissemination of agreed standards of care and general knowledge in the area of expertise; and increased profile and recognition of the participants." Basically, these groupings should attract the best experts, as well as patients and decrease the burden of travel for patients. They should also better position members for applying for funding or other types of support.
  • In the past, these sorts of groupings have arisen spontaneously or in an ad hoc way among researchers, in a response to available funding. But such networks are often highly focused and unsustainable in the long term.
  • The problem with grouping rare diseases by treatment area (e.g. gene therapy) is that the fundamental problem that many rare diseases don't have a designated treatment, isn't addressed.
  • So the ERN's ended up going with the following scheme, which is clinically based, and based on studying the pros and cons of other above mentioned schemes like EURORDIS and Orphanet. They decided on thematic networks of rare diseases such as eye diseases, endocrine diseases, cancers and tumors, bone diseases, and urogenital diseases.
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Rare Diseases - Compelling Facts

Most clinical trials for rare diseases have an American or European perspective with limited information on non-Caucasians. Thirty percent of children who are diagnosed with rare diseases succumb before they are five years old. In addition, 90% of rare diseases are not diagnosed correctly.

Compelling Facts About Rare Diseases

  • Ninety percent of rare diseases are misdiagnosed. The trend has been ongoing for the last 10 years. As patients continue being misdiagnosed, they keep getting worse to a point where the disease reaches an irreversible stage.
  • A majority of clinical trials have a European or American perspective. For instance, a German company called Rolf, which has a diagnostic portfolio of 3500 diseases notes that 95% of its database refers to information from Europe and the US and "less than 5% are non-Caucasian." The number of clinical trials on non-Caucasian is worrying given that genetic makeup varies with different populations.
  • As it stands, approximately 24% of people with rare diseases have been diagnosed at early stages and received treatment. This shows the importance of early stage detection, however, a huge percentage of people suffering from rare diseases unknowingly suffer.
  • The impact of rare diseases can be devastating to the affected individuals, their friends, and families. Thirty-percent of children who suffer from rare diseases die before they are five years old.
  • About 95% of rare diseases do not have approved treatment. Therefore, a diagnosis can be crushing to patients and their loved ones instead of bringing relief and assurance. This has an emotional toll on them.
  • Fifty percent of rare diseases among children and adults who suffer from them eventually lead to adult care. This is due to lack of resources and information, the high cost of care, and challenges in accessing medical expertise.
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Rare Diseases - Financial and Societal Impacts

The median annual cost of the top 100 orphan drugs in the United States is $109,723. The spending on orphan drugs in the United States was $43 billion in 2017. It takes an average of 7.6 years to correctly diagnose a rare disease and typically caregivers spend 8.9 years providing care.

Economic Impact

  • In 2018, the average per-patient annual cost of the top 100 orphan drugs in the United States was $150,854 as against $33,654 for non-orphan drugs. The mean per-patient annual cost of the top 100 orphan drugs grew at 4.2% CAGR between 2014 and 2018.
  • In 2018, the median per patient annual cost of the top 100 orphan drugs in the United States was $109,723 as against $15,702 for non-orphan drugs. The median price differential between orphan and non-orphan drugs decreased between 2014 and 2018.
  • Total drug spending in the United States was $451 billion. Orphan drugs accounted for 9.6% ($43 billion) of overall drug sales in the United States in 2017.
  • In the United States, orphan drugs get marketing exclusivity of seven years from approval, a 50% "tax credit on R&D costs", phase 1-3 R&D grants for clinical trials, and waived user fees.
  • Half (51%) rare disease caregivers experience "high levels of financial strain", and 75% worry about being able to pay for care giving expenses. Most (86%) of caregivers have faced "financial hardships" owing to their care giving.
  • Rare caregivers curb household spending (81%), are unable to make long-term financial savings (62%), and use up personal savings (59%). Nine percent have even filed for bankruptcy.
  • Only one in three (33%) rare disease caregivers rely on paid help.

Disease-Specific Economic Impact

  • The economic impact of Duchenne muscular dystrophy (DMD) "in terms of hospital stays, caregivers’ work absences and lost productivity" is $1.21 billion.
  • The productivity cost of Multiple Myeloma (MM) over the period 2020-2029 will be $5 billion. The annual health care cost is $280,000.
  • The productivity cost of Sickle Cell Disease (SCD) over the period 2020-2029 will be $2.1 billion. The annual health care cost is $30,000.
  • The productivity cost of Hemophilia A (Hem A) over the period 2020-2029 will be $0.4 billion. The annual health care cost is $200,000.

Social Impact

  • In the United States, it takes an average of 7.6 years for a rare disease to be diagnosed correctly. In this period a rare disease patient usually visits eight different doctors and receives a couple or more misdiagnoses.
  • Ninety-five percent of rare diseases have no approved treatments; 80% of rare diseases are genetic. Learning of the rare disease condition is very overwhelming for both patients and families and has a heavy toll on them emotionally.
  • Nearly two in three (62%) caregivers provide care to children aged<= 18 years; the "average age of the care recipient" is 20.9 years. Caregivers are usually immediate relatives: 59% are parents of <=18 year children, 17% are parents of adult children, and 14% are partners or spouses.
  • Only 38% of caregivers believe that the local hospital can handle the rare-disease-care recipient's condition; 34% have difficulty accessing symptom-management treatments, and 31% have trouble accessing treatment for the underlying disease. Less than half (48%) of doctors have discussions about what is required to provide care to a rare disease patient. Rare disease caregivers often research the disease themselves and become experts (89%) educating medical professionals about the disease.
  • Rare disease caregivers provide care for an average period of 8.9 years, more than twice as much as general caregivers. On average, they spend 37 hours per week providing care, 12 hours more than general caregivers. The lack of support and outreach "fundamentally alters" their life for nearly a decade.
  • Caregiving impacts every aspect of caregivers life. Two in three (65%) caregivers work, nearly all of whom report that it affects their work life; 90% of working caregivers report going late to work or leaving early to provide care. Ten percent of caregivers are students themselves and have trouble coping with school.
  • Two in three (65%) of rare caregivers report that they find the process emotionally stressful; 41% report poor "mental and emotional health", and 37% report physical strain. Fifty-eight percent report difficulty caring for their own physical health, and 30% report not having good physical health.
  • Fifty-one percent of rare caregivers report having "difficulty maintaining friendships" and 53% report "feeling alone".

Research Strategy

The research findings provided pertain to the United States. The government is yet to study the total economic and social impact of rare diseases in the United States. There is a request to include "$1.5 million for a Rare Disease Burden Study in the Senate’s Fiscal Year 2020 Labor, Health and Human Services, Education Appropriations Bill". While data specific to the economic burden of certain rare diseases was available, there was no similar publicly available report found for rare diseases as a whole.
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Rare Disease - Key Challenges

Four challenges in the rare disease space, globally, are: getting a diagnosis, financial concerns, social isolation, and limited approved therapies. A more detailed analysis is presented below.

Diagnosis Challenges

Financial Challenges

Social Isolation Challenges

  • Many of those active in rare diseases are impelled not just by the idea of finding new cures and treatments, but also have a deep wish to end the sense of anguish and loneliness that patients and their families often feel when they are told the source of their symptoms.
  • “Not having a diagnosis, the feelings that it brings of isolation and exclusion and of not being understood — that is very difficult,” says Virginie Bros-Facer, Scientific Director at EURORDIS-Rare Diseases Europe, a "non-profit alliance of over 800 rare disease patient organizations from 70 countries that work together to improve the lives of people living with a rare disease in Europe. "
  • The occurrence of mental health disorders is much higher in individuals with a rare disease, compared to the general population.
  • Because of their uncommonness, rare diseases are often not understood by the public and ignored by major pharma companies. The result for sufferers can be both acute loneliness and social isolation; for kids and teens, already at risk because of their age, learning to manage their rare disease with its isolating tendencies can be particularly difficult.

Limited Approved Therapy Challenges

  • Even when finally diagnosed, in far too many cases the odds are long that rare disease sufferers will actually receive effective treatment. The fact is that for 90% of rare diseases, there is no approved therapy.
  • Only sixty percent of rare disease treatments make it into Canada, and the majority of them get approved up to six years later than in the USA and Europe.
  • It is estimated that 95 percent of rare diseases do not yet have a single FDA-approved treatment.
  • While off-label use has proved to be an important tool in the physician’s toolkit, the Food and Drug Administration (FDA) released a memo highlighting the increased likelihood of adverse events from off-label use (often due to lack of sufficient evidence) and points out that with off-label use there is a greater potential for wasted health care dollars.
  • "Low patient numbers, an incomplete understanding of the disease pathology, phenotypic heterogeneity, and a lack of established endpoints are barriers to efficient and effective clinical trials, which can make meeting regulatory requirements for drug approval challenging."
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Rare Diseases - Innovations and Developments

Important recent innovations in the treatment of rare diseases include new treatments for multiple sclerosis, narcolepsy, Fabry disease, and cystic fibrosis.

Innovation in the Treatment of Multiple Sclerosis (MS)

  • In 2016, the Multiple Sclerosis Society-funded International Consortium of MS Genetics published a list of "200 genetic variations linked to MS". This finding of multiple relevant genetic variations made it possible to find new ways that genes may "make people susceptible to developing MS."
  • This finding of 200 genetic variations linked to MS is significant because researchers now have a kind of road map of specific gene variations to address. Researchers no longer have to start from scratch to identify the genes that affect development of MS in a particular patient. The finding is also significant because knowing the gene variations will help researchers to "find better treatments and prevention" directed at specific gene variations.
  • In the last three years, three new drugs using this approach have been approved by the Food and Drug Administration (FCA) for the treatment of MS. In 2017, the FDA approved Ocrevus (ocrelizumab) as a "first disease-modifying therapy for primary progressive MS, and also as a therapy for relapsing MS".
  • In 2018, the FDA approved expanding the use of Gilenya for children with relapsing MS. Gilenya was the "first therapy specifically approved to treat pediatric MS."
  • In 2019, the FDA approved prescribing oral Mavenclad (cladribine) and oral Mayzent (siponimod) for adults with particular forms of MS.

An Innovation in the Treatment of Narcolepsy

  • Because of studies conducted during the past 10 years, researchers have grown in their ability to understand "the underlying biology of narcolepsy...." This new understanding has resulted in the development of a new treatment approach using substances that affect a particular brain chemical: histamine. Instead of relying on increasing dopamine--the current approach to treating narcolepsy-- the new research indicates that increasing histamine (another brain chemical) also can be effective in treating narcolepsy. Pharmaceutical companies are developing drugs to block a brain receptor that stops the release of histamine, thus allowing more histamine to be produced.
  • This approach is one of the few new ways to deal with narcolepsy.

Innovation in the Treatment of Fabry Disease

  • The genetic disorder called Fabry disease "causes severe and irreversible organ damage due to the buildup of a fatty substance called globotriaosylceramide (Gb3 or GL-3) inside cells. This accumulation is caused by a deficiency of an enzyme called alpha-galactosidase A." A new treatment with chaperones "can help cells digest Gb3." If the Gb3 buildup is reduced, the organ damage can be reduced.
  • "Chaperones are small molecules that assist proteins in becoming functional...."
  • Chaperone treatment is viewed as a "novel therapy" that has potential to relieve the pain of Fabry disease. The older, more customary treatment is called enzyme replacement therapy and has dominated the market through sales of the drugs that accomplish such treatment.

Innovation in the Treatment of Cystic Fibrosis

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Rare Diseases - Major Conferences

The European Conference on Rare Diseases & Orphan Products (ECRD), ICORD's Annual Conference and NORD's Rare Summit are three major conferences, globally, that address rare disease challenges and advocate for new innovations in the space.

The European Conference on Rare Diseases & Orphan Products (ECRD)

  • The European Conference on Rare Diseases & Orphan Products (ECRD) was selected as one of the major conferences globally that addresses rare disease challenges and innovations because it is the world's largest patient-led rare disease event.
  • Notably, the ECRD attracts over 800 participants from more than 50 countries, including representatives from its organizers, EURODIS and Orphanet Inserm, as well as notable keynotes, such as Beate Hartinger-Klein, Austria’s Federal Minister of Health and Social Affairs, and Martin Seychell, the Deputy Director of General for Health and Food Safety of the European Commission.
  • The event also has a long list of sponsors, including AFMtelethon and the Health Programme of the European Union.
  • Meanwhile, the biennial event appears to have a three-pronged purpose: (1) to facilitate learning about the latest "advances and challenges" in the rare disease space from over 100 expert speakers, (2) to help shape the future of rare disease treatment globally and (3) to facilitate networking among the rare disease community.
  • Although conference topics vary by each event, the upcoming 2020 ECRD is expected to highlight subjects including the rare disease patient journey as well as potential innovations in the rare disease space by 2030.

ICORD's Annual Conference

  • The annual conference hosted by the International Conference on Rare Diseases and Orphan Drugs (ICORD) was also identified as a major worldwide event in this space given its large and international attendee base as well as the conference's longstanding history.
  • Specifically, past conferences have attracted over 700 attendees, and have included notable guests such as Baoguo Tian, the Deputy Director-General of the Chinese Department of Sciences, and the Professor Shuyang Zhang, the Vice President of Peking Union Medical College Hospital.
  • Although sponsorship varies by conference year and location, past sponsors have included Pfizer, BGI Genomics, Amgen and Shire.
  • The purpose of the conference and its parent organization is to improve patient welfare globally through "better knowledge, research...education and awareness."
  • Additionally, topics from past conferences have included the "remaining unmet needs" in rare diseases as well as global challenges in the rare disease space.

NORD's Rare Summit

  • The Rare Summit hosted by the National Organization for Rare Disorders' (NORD) was similarly selected as a major conference discussing industry challenges and innovations given that it boasts one of the largest attendee base as well as a variety of prominent speakers.
  • Most recently in 2019, the Rare Summit included a record 900 participants, including keynotes by Acting FDA Commissioner Norman Sharpless and Health and Human Services Secretary Alex Azar.
  • Additionally, the annual event has a variety of high profile sponsors, including Sanofi Genzyme, Biogen, Genentech and McKesson.
  • Meanwhile, the purpose of the annual conference is to "drive innovation and collaboration" in the rare disease space to develop better outcomes for impacted families.
  • Related topics within specific conferences have included drug pricing, technology advancements and current research in rare diseases.
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Rare Disease - Governmental Agencies

Four major global governmental agencies were identified in this research: the European Commission's Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases; the United Kingdom's Rare Disease Policy Board; the U.S. Office of Rare Disease Research; and Canada's Health Canada. These organizations and their respective roles area discussed in more detail below.

Government Agency 1: The EU Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases (European Union)

  • The Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases ("the Steering Group") is a branch of the European Commission. It supports European member states to reach the health targets outlined in Europe's Sustainable Development Goals. The group focuses on four main policy areas and one of those is rare diseases.
  • The Steering Group aims to improve access to diagnosis of rare diseases, provide information about rare diseases to the public, and improve access to rare disease treatment options. Examples of recent accomplishments of the Steering Group include recommendations to the European Commission for measures that would improve sharing diagnostic resources among member states (2015), recommendations to member states to better incorporate rare diseases into their domestic health policies (2016), and financing a research project aimed at better informing European member states' policies with respect to rare diseases (2017).
  • In addition to continuing to coordinate member state action on rare diseases, the Steering Group plans to fund research on rare diseases through the program Horizon 2020. The program will make €900 million available for research on rare diseases over the next 7 years.

Government Agency 2: U.K. Rare Disease Policy Board (United Kingdom)

  • The U.K. Rare Disease Policy Board is responsible for overseeing the implementation of the UK strategy for rare diseases in the four countries that make up the U.K.: English, Wales, Scotland, and Northern Ireland. The board is made up of a number of stakeholders, including individuals from the national Department of Health and Social Care, the National Health Service, the Scottish, Welsh, and Northern Irish governments. It also includes doctors and patients suffering from rare diseases.
  • In the past few years, the policy board has had a number of accomplishments, bringing the UK closer to fully implementing their rare disease strategy. The board completed implementation plans in each of England (2018), Scotland (2014), Wales (2015), and Northern Ireland (2015). The board also supported a rare disease forum conference in 2017 that brought together industry, policy-makers, patients, and researchers. And, in 2018, they supported a survey of patients with rare diseases, the results of which will inform the work of the policy board.
  • Future goals include participating in the creation of a National Genomics Board which would support gene research, improving collaboration between the four nations of the United Kingdom, working to create platforms that improve the sharing of research data, and maintaining partnerships with European research communities as the UK leaves the European Union.

Government Agency 3: Office of Rare Disease Research (United States)

  • The Office of Rare Disease Research (ORDR) is an agency established by US federal government legislation under the National Institute of Health (NIH). The office is located within the NIH's National Center for Advancing Translational Sciences (NCATS). It is responsible for coordinating and overseeing NIH activities related to rare diseases.
  • Among the primary tasks of the ORDR is maintaining a database on rare diseases, liaising and collaborating with international rare disease organizations, and responding to information requests from other government departments to inform rare disease policy. The office oversees several programs related to rare diseases, including the Genetic and Rare Disease Information Center (GARD), the Rare Disease Registry Program (RaDaR), and the Rare Disease Clinical Research Network (RDCRN). GARD provides information to the public about rare diseases, RaDaR guides rare disease researchers with keeping and maintaining databases and registries of rare diseases, and RDCRN supports researchers to conduct and disseminate high quality research on rare diseases.
  • Some recent accomplishments include providing $1.5 million in grant funding in 2019 for clinical researchers working on rare diseases, launching a rare disease awareness contest in 2018, and, in 2016, launching the Biomedical Data Translator to make research data on rare diseases more accessible.
  • The office and its programs have several goals for the future. One is to move away from an approach where one treatment to rare diseases is developed at a time, and instead pursue an approach that looks at disease commonalities. They hope this strategy will allow treatment development to happen more efficiently. Another goal is to support research on rare diseases by developing patient registry systems that are scalable and patient-centered.

Government Agency 4: Health Canada (Canada)

  • Health Canada is a Canadian federal government agency that is broadly responsible for ensuring that Canadians stay healthy. It is responsible for advising on and creating health policy throughout the country, providing health information to the public, conducting health research, and approving food and products for sale in Canada.
  • With respect to rare diseases, Health Canada advises and makes national drug policy and provides information to the public about rare diseases and various treatment options. They also play an important role in making treatments available for rare diseases because they are the body that approves drugs to be sold in Canada.
  • In the past 5 years, Health Canada has harmonized regulatory requirements for drug manufacturers with other international jurisdictions so companies applying to have their rare disease drugs approved can apply only once. For example, Health Canada developed a common drug approval application portal with the US Food and Drug Administration. This has improved the efficiency of the orphan drug approval process.
  • In 2016, Health Canada also launched a review of the regulations around the approval of drugs for rare diseases in Canada. The aim of that review was to find opportunities to make the regulatory process for these drugs even more efficient. Then, in 2017, Health Canada approved 16 drugs for the Canadian market that are used to treat rare diseases.
  • The Canadian government, through Health Canada, plans to do more for the future: they plan to create a national drug agency that would help coordinate bringing access to orphan drugs to Canadians and they further plan to invest $1 billion over 2022 and 2023 to fund a national strategy for rare diseases that would make treatments for rare diseases more accessible.

Research Strategy

The research team defined government agencies as any agency that was directly affiliated with a governing body—either national or international. This included government departments (like Health Canada), as well as institutions directly created by, or linked to, national or international governments, like the Rare Disease Policy Board in the U.K., and the E.U. Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases. All organizations that were established by government legislation were also considered government agencies, which includes the U.S. Office of Rare Disease Research.

The research team was asked to look for "major" governmental agencies. Agencies were determined to be "major" when they influenced national or international policy and outcomes for jurisdictions that had populations greater than 30 million people. A population size of 30 million or greater was chosen because less than 20% of countries have populations this big; these countries represent the top fifth largest countries by population.

Each of the four organizations listed above directly influence national policies and have international reach. The European Steering Group influences polices of the 28 nations that are members of the European Union. The U.K. Rare Disease Policy Board influences policy in each of the 4 countries that make up the United Kingdom. Both the Office of Rare Disease Research in the U.S. and Health Canada influence national policy in their respective jurisdictions and also have international collaborations. Further, the populations for each of the jurisdictions represented by the above organizations exceeds 30 million: Canada's population is about 35 million, the U.K.'s population is about 65 million, the population of the U.S. is about 326 million, and the population of all the European member states together is about 513 million. Thus, it was determined that each of the above organizations can be considered to be "major" governmental agencies.

The research also required that we find agencies that "deal with" rare diseases. We determined that an agency "deals with" rare diseases if it plays a role in any of the following functions related to rare diseases: collecting data or conducting research, sharing data, engaging in actions that support prevention or treatment, making or advising policy, or providing information to the public. Among other actions, all the organizations included here make and advise on policy for rare diseases. They also all provide information to the public. Thus, they all met the criteria for inclusion.
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Rare Diseases - Non-Profit Organizations

EURORDIS, International Federation for Spina Bifida and Hydrocephalus (IF-SBH/IF), and Rare Diseases International (RDI) are some major non-profit organizations, that deal with rare diseases.



  • The organization's website can be found here.
  • EURORDIS is a "non-governmental patient-driven alliance of patient organizations representing 884 rare disease patient organizations in 72 countries".
  • The organization, through its members, represent 30 million people in the European region.
  • Its mission is to improve the living conditions of people with rare diseases, through patient advocacy, medicines & therapies, healthcare, social policies & services, research policy & actions, patient empowerment & training, and information & networking.


  • In the last three years, EURORDIS successfully organized the European Conference on Rare Diseases & Orphan Products (ECRD), which had 857 participants from 58 countries. The conference met the expectations of 84% of attendees according to the evaluation survey.
  • The organization has been able to reach over 2,500 patient groups in 2018, from 1,800 in 2016.
  • It has also grown its member patient organizations from 747 in 2016 to 826 in 2018.

Future Goals

  • In the next decade, EURORDIS is looking to prioritize its advocacy for rare diseases, specifically to promote the implementation of policy recommendations and an "information & harmonized coding" system for rare diseases.
  • Other key focus areas under its future advocacy goals include advocacy for the improvement of patient access to rare disease therapies, advocacy for the improvement of access to care for patients with rare diseases, and advocacy for patients rights to cross-border healthcare.
  • The organization is looking to increase patient empowerment, including building its patient advocate network and its capacities, raise more awareness and provide more information on rare diseases.
  • Also, the organization is looking to encourage more patient engagement in decision-making, especially in healthcare, social care, research, and lifecycle development.

International Federation for Spina Bifida and Hydrocephalus (IF-SBH/IF)


  • The organization's website can be found here.


  • IF has successfully reached 8,165,151 people and gathered 866 supporters through its campaign organized for the World Birth Defects Day 2018.
  • Since 2016, it has visited over 1,140 children, treated over 2,166 children through its local partners in Africa (Tanzania, Kenya, Uganda, Zambia and Malawi), distributed over 10,611 folic acid tablets, and reached out to more than 1 million women.
  • The organization has also been able to reach up to 415,960 people through its World Folic Acid Awareness Week.

Future Goals

For the 2018-2022 period, IF is focusing its plans on two main areas;
  • It is looking to "consolidate and strengthen" the rights of patients with spina bifida and hydrocephalus.
  • It is also looking to encourage the "primary prevention" of hydrocephalus and neural tube effects.
  • The organization intends to accomplish these goals through political advocacy, research, community building, human rights education, and raising awareness.

Rare Diseases International (RDI)


  • The organization's website can be found here.
  • RDI is the "global alliance" for people with rare diseases. It caters to all nationalities and all types of rare diseases.
  • The organization works globally with other rare disease organizations and rare disease-specific federations.
  • It is aimed at uniting, expanding, and reinforcing the movement of rare disease patient advocates and organizations.


  • RDI became a full-fledged NGO in November 2018 under the French law in France. It also signed an MOU with EURORDIS for its continuous support for 5 years (2019-2023).
  • The organization has grown from 20 member organizations in 2015 to 57 member organizations by the end of 2018.
  • Its representation of rare disease patients has spread to 100+ countries globally, through its member organizations.

Future Goals

  • Although RDI is yet to release its latest action plan after that of 2019, the organization has stated that its vision is to improve recognition and support, health, social services and provide a better life for people living with rare diseases globally.
  • In the future, the organization will continue to promote rare diseases as an "international public health and research" priority.
  • It will also be looking to improve the capacity of its members through networking, information exchange and mutual support.

Research Strategy

To fulfill this request, we commenced our research for an association of NGO's that deal with rare diseases. We were able to identify the NGO Committee for Rare Diseases, which featured some rare disease NGO organizations represented on their board. For this request, we defined "major non-profit organizations" as those who operate in over 20 countries globally. We have provided a report with all our findings above.
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Rare Diseases - For Profit Organizations

Global for-profit organizations specializing in rare diseases are Alexion Pharmaceuticals, BioMarin Pharmaceuticals, and CSL Behring. These companies have identified themselves on their websites as organizations that develop drug therapies for patients suffering from serious and rare genetic and spontaneous diseases.

Alexion Pharmaceuticals, Inc.

  • Alexion's website is alexion.com.
  • Alexion is a global biopharmaceutical company that serves patients suffering from rare diseases through research and development. The company works with patients in 50 countries worldwide.
  • In 2019, the company's product SOLIRIS was FDA approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients. The approval stems from a Phase 3 treatment for NMOSD which resulted in 98% of patients treated with the drug not relapsing.
  • In 2019, SOLIRIS also received approval in Japan for NMOSD treatment. It is the first and only medication approved for NMOSD in Japan.
  • In the past 5 years (2015-2020), Alexion's products have received approval in Europe, Japan, and the United States. Usually, the organization's products are the first and only in approved countries and are designed for several rare diseases.
  • Alexion is planning its Phase 3 research for a new drug that will slow down the progression of ALS in patients. The organization has submitted the drug application to the FDA intending to receive approval to begin trials.

BioMarin Pharmaceutical, Inc.

  • BioMarin's website is biomarin.com.
  • BioMarin is a global leader in biopharmaceuticals for rare genetic diseases. The organization's patient population is mostly made up of children who suffer from extremely rare medical conditions.
  • In September 2015, BioMarin's first Hemophilia A patient was enrolled in trials for gene therapy. This project has since made significant progress in the development of gene therapy drugs for patients with severe Hemophilia A.
  • In April 2017, Brineura, a BioMarin drug, received FDA approval for treatment in children with a form of Batten disease, CLN2. This drug is the first treatment for CLN2 disease in children.
  • BioMarin plans to continue research in gene therapy for Hemophilia A patients. According to the President of Worldwide Research and Development Dr. Hank Fuchs, BioMarin plans to release a four-year update mid-2020 and provide a third-year followup after low levels of expression are achieved later this year.

CSL Behring

  • CSL Behring's website is cslbehring.com.
  • CSL Behring merged with several companies that are focused in the biotechnology sector including Aventis Behring and Nabi, a plasma collection company. The company is a global biotech leader that develops solutions for rare autoimmune diseases, hereditary disorders, chronic disorders, and more.
  • In 2016, CSL's drug AFSTYLA was approved by Health Canada for treatment of Hemophilia A. Its clinical trials resulted in a median annualized spontaneous bleeding rate of 0.
  • In 2017, the FDA approved HAEGARDA, the first preventive treatment for hereditary Angioedema. The drug reduced attacks by 95% in patients with life-threatening genetic disorders.
  • According to the Head of Research and Development Dr. William Mezzanotte, CSL's goals are grounded in building on its plasma therapies through the emergence of new medicines.
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Rare Diseases - Academic Institutions

Rare disease research happens at multiple academic institutions around the world. Following are a few of the leading institutes that work with rare diseases.

U Mass Medical School, founded in 1962, is Massachusetts' first and only public health science center. It is one of The United States' leading schools for primary medical training as ranked by US News and World Report. The Weibo Institute provides a unifying structure for multiple departments within the medical school to work on rare diseases research. Research at this institute focuses on about 60 of the more than 7000 rare diseases. The institute emphasizes:
Gene Therapy: putting DNA or RNA into cells to treat disease
Genome Editing: correcting genetic defects in DNA in order to cure disease

Recent accomplishments include:
Development of gene therapy for Canavan Disease, a first human trial for the treatment, and the licensing to a pharmaceutical corporation for drug development.

Future Goals for the Weibo Institute include:
Continuing to research Canavan Disease, diseases affecting neurological and metabolic functioning, and those that affect multiple bodily systems.

The University of Pennsylvania's Perelman medical school was the first US medical school and first teaching hospital. Perelman emphasizes research, patient care and education.

The Orphan Disease Center's research areas include:
Pediatric Epilepsy & Neurodevelopmental Disorders
Lysosomal Storage Disorders
Motor Neuron Disorders
Liver Metabolic Disorders

The Orphan Disease Center also favors a collaborative research approach with corporations and patient groups.

Recent Accomplishments include:
Granting of $17.2 million in research funds since 2011
Granting of $2.2 million from the Million Dollar Bike Ride
Contributing to the expansion of research on rare diseases through hosting of symposia

Future Goals Include:
Developing therapies and technologies for treating multiple diseases
Identifying and funding promising therapies
Helping overcome obstacles in development of drugs used to treat rare diseases
Continuing to develop patient registries to advance understanding of rare diseases

Oxford-Harrington is a new institute, founded in 2019. This large organization is a collaboration between The University of Oxford and the Harrington Discovery Institute at the University Hospitals. It features a
collaborative approach, with over 250 scientists working on over 350 rare diseases across more
than 20 departments. The centre offers opportunities for networking and research.

Recent Accomplishments Include:
Since this is a new institute, its main accomplishment has been its conference.

Future Goals Include:
Restructuring the research process in order to efficiently address how to develop treatments for the large number of rare diseases in dire need of a cure.
Partnering with patient organizations to provide support.
Continuing to explore specific gene therapies,


From Part 01
From Part 04
  • "In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people. Rare diseases, as a whole, affect about 25 million people in the United States and about 400 million worldwide. "
  • "Rare diseases include many single gene disorders such as Huntington disease and Duchenne Muscular Dystrophy; many childhood and adult diseases, such as Guillain-Barré syndrome and Crohn’s disease; and some childhood cancers and infectious diseases. "
  • "The economic impact of rare diseases is substantial not only for affected patients and their families, but for society as a whole."
  • " In a survey of patients and caregivers in the USA and UK, patients reported that it took on average 7·6 years in the USA and 5·6 years in the UK to get a proper diagnosis, during which time patients typically visited eight physicians (four primary care and four specialist) and received two to three misdiagnoses. As there is no approved treatment for 95% of rare diseases, a diagnosis can be a crushing reality check for patients and their families, rather than bringing hope and reassurance. As such, rare diseases impose a considerable emotional toll on patients and their caregivers. Other challenges include a lack of information and resources, the financial cost of care, and difficulty in accessing appropriate medical expertise, which is compounded by a lack of specialist training programmes for medical professionals."
  • "93% of more than 7,000 rare diseases have no FDA-approved treatment or cur"
  • "On average, it takes 8 years to properly diagnose an individual with a rare disease. "
  • "While there are an estimated 30 million total Americans suffering from rare diseases, data is limited as these small underserved patient populations span more than 7,000 unique diseases. "
From Part 05
From Part 06
  • "A report by the global investment bank Torreya looks at the most common types of rare diseases that are a focus for therapeutic companies around the world: Multiple sclerosis emerges above all others, at 90 patients per 100,000 people. Narcolepsy—intermittent, uncontrollable episodes of sleepiness—affects 50 patients per 100,000. Primary biliary cholangitis, the damage of bile ducts in the liver, affects 40 people in 100,000. Rounding out the top five orphan diseases are Fabry disease (30 patients per 100,000), and cystic fibrosis (25 patients per 100,000). One catch behind these stats? There’s actually no universal definition of what constitutes a rare disease. This means prevalence data like the above is often inconsistent, making it difficult to record the precise rate of natural occurrence."
  • "2016 - Society-funded International Consortium of MS Genetics identifies 200 genetic variations linked to MS, offering new leads to how genes and other factors that make people susceptible to developing MS "
  • "2017 - FDA approves Ocrevus (ocrelizumab) as first disease-modifying therapy for primary progressive MS, and also as a therapy for relapsing MS"
  • "2018 - FDA approves expansion of the use of Gilenya to include children and adolescents 10 years of age or older with relapsing MS, the first therapy specifically approved to treat pediatric MS"
  • "2019 - FDA approves oral Mavenclad (cladribine) for adults with relapsing forms of MS, and also approves oral Mayzent (siponimod) for adults with clinically isolated syndrome (an initial neurological episode) and relapsing forms of MS"
  • "Studies are uncovering lifestyle factors that people can change – such as smoking, childhood obesity, and vitamin D levels – that may reduce the risk of the next generation developing MS."
  • "Researchers have found gene variations that combine to influence whether a person is more susceptible to MS, and are pursuing these clues to help understand what causes MS and how to find better treatments and prevention."
  • "Over the past 10 years, researchers have made great advances in understanding the underlying biology of narcolepsy, and these insights are now leading to new and possibly more effective treatments for narcolepsy."
  • "Most current medications for narcolepsy improve alertness by increasing the amount of dopamine in the brain, but histamine is another brain chemical that is very effective for improving alertness. Normally, histamine levels are kept low by signaling through the histamine H3 receptor. Pharmaceutical companies are developing several compounds that block the H3 receptor, permitting histamine levels to rise. "
  • "Fabry disease is a rare genetic disorder that causes severe and irreversible organ damage due to the buildup of a fatty substance called globotriaosylceramide (Gb3 or GL-3) inside cells. This accumulation is caused by a deficiency of an enzyme called alpha-galactosidase A. Chaperone therapy is a new investigational method that can help cells digest Gb3."
  • " Chaperones are small molecules that assist proteins in becoming functional by helping them take the correct shape and stay stable. With chaperone therapy, some faulty forms of alpha-galactosidase A can be corrected and delivered to the lysosomes so that the excess Gb3 can be broken down."
  • "Cystic fibrosis (CF), a life-threatening multiorgan genetic disease, is facing a new era of research and development using innovative gene-directed personalized therapies. The priority organ to cure is the lung, which suffers recurrent and chronic bacterial infection and inflammation since infancy, representing the main cause of morbidity and precocious mortality of these individuals. After the disappointing failure of gene-replacement approaches using gene therapy vectors, no single drug is presently available to repair all the CF gene defects. The impressive number of different CF gene mutations is now tackled with different chemical and biotechnological tools tailored to the specific molecular derangements, thanks to the extensive knowledge acquired over many years on the mechanisms of CF cell and organ pathology. "
  • "2019 The FDA approves the first triple-combination therapy, elexacaftor/tezacaftor/ivacaftor (Trikafta™), for people with CF ages 12 and older who have at least one copy of the F508del mutation, regardless of their second mutation. The approval of this drug means that approximately 90 percent of people with CF could eventually have a highly effective treatment for the underlying cause of their disease. "
  • "2019 The FDA approves the use of ivacaftor for children as young as 6 months who have one of 38 mutations. 2019 The FDA approves the use of tezacaftor/ivacaftor for children ages 6 to 11 who have two copies of the F508del mutation or a single copy of one of 26 specified mutations. "
  • "According to the U.S. National Library of Medicine, Fabry’s disease affects an estimated 1 in 40,000 to 60,000 males. Patients with Fabry’s disease suffer from severe pain of extremities, heart disorder, kidney failure, disabling gastrointestinal symptoms and stroke."
  • "Increasing prevalence Fabry's diseases coupled with increased adoption of novel therapies such as chaperone treatment is one of the major driving factors for the growth of the global Fabry's disease treatment market. "
  • "Current treatments: Enzyme Replacement Therapy (ERT) · Substrate Reduction Therapy (SRT) · Chaperone Treatment"
  • "In 2018, among treatment, enzyme replacement therapy dominated the global Fabry's disease treatment market due to the massive sales of Fabrazyme and Replagal and approvals of promising pipeline candidates. "
From Part 08
From Part 10
  • "Alexion (NASDAQ: ALXN) is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development and commercialization of life-changing therapies."
  • "Alexion has 3,000 passionate and dedicated employees serving patients in 50 countries around the world."
  • "These patient populations are mostly children, suffering from diseases so rare, that the entire patient population can number as few as 1,000 people worldwide."
  • "Since then, CSL has acquired a number of companies. They include: Aventis Behring, which is now known as global biotechnology leader CSL Behring, U.S. plasma collector Nabi, which helped to form the world's premier plasma collection company in CSL Plasma, the Novartis influenza vaccine business, now integrated and known as Seqirus, the world's second largest influenza vaccines company and Calimmune, a leader in gene-modification and cell delivery technology. "
From Part 11
  • "University of Massachusetts Medical School (UMMS), the commonwealth’s first and only public academic health sciences center. "
  • "Gene therapy refers to the delivery of a nucleic acid, such as DNA or RNA, into a patient’s cells as a treatment for a disease."
  • "Genome editing aims to correct the genetic defect in the patient’s DNA (or genome) and thereby cure the disease."
  • "research on gene therapy, which gradually culminated in a series of discoveries: the identification of a viral vector that can be used for delivering gene therapy to the CNS and treating Canavan disease with intravenous injection; the first preclinical proof-of-concept Canavan disease gene therapy in a mouse model of the disease; and the first-in-human expanded access trial on a patient with Canavan disease. "
  • "Internationally recognized Huntington’s disease researcher Neil Aronin, MD, led an afternoon of presentations detailing advances made by scientists at UMass Medical School in the quest to find a treatment for the deadly neurological disorder"
  • "Researchers at UMass Medical School and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have developed a strategy to treat two of the most common inherited blood diseases—sickle cell disease and beta thalassemia—applying CRISPR/Cas9 gene editing to a patient's own blood stem cells."
  • "The U.S. Food and Drug Administration has approved patisiran, a novel RNAi therapeutic for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients."
  • " Working closely together in this uniquely collaborative environment, they seek to identify and develop solutions to devastating ailments, from heart disease to ALS. Their efforts have the potential to unlock therapies or even cures for people with a variety of rare diseases."
  • "As the nation's first medical school and home to the first teaching hospital, the Perelman School of Medicine has a long tradition of academic excellence and scientific discovery. "
  • "Our mission is to advance knowledge and improve health through research, patient care, and the education of trainees in an inclusive culture that embraces diversity, fosters innovation, stimulates critical thinking, supports lifelong learning, and sustains our legacy of excellence. "
  • "The ODC does not see or treat patients, rather we support and fund research in pursuit of therapeutic developments for rare diseases."
  • "The Orphan Disease Center has a vested interest in various rare disease areas that show promise for therapeutic development."
  • "To explore partnership opportunities, please contact Dr. Jim Wilson."
  • "The Orphan Disease Center works with patient groups around the world, emphasizing disorders with significantly underserved populations."
  • "The ODC offers over 50 grant opportunities in 30+ disease areas annually to researchers across the globe, as well as within the Penn and CHOP communities. Since 2011, our grant programs have funded $17.2 million in rare disease research."
  • "36 researchers across 24 institutions were awarded grants for 29 different rare diseases (listed below), with money raised from the 2019 Million Dollar Bike Ride. Over $2.2 million dollars were awarded in total. "
  • "Visit our Events Page for information about upcoming symposia. "
  • "The Orphan Disease Center will develop transformative therapies using platform technologies that can be deployed across multiple rare diseases. We will emphasize disorders with substantial unmet need independent of their incidence and will strive to assure access to patients of all populations. "
  • " The data collected in these registries is essential for understanding rare diseases and accelerating the development of new treatments."
  • "The Oxford Rare Disease Initiative (ORDI) brings together this expertise to create an extensive rare disease network, and provides assistance in establishing collaborations between Oxford rare disease researchers, industry, patient organisations and funders. "
  • "The 2nd Biennial Oxford Rare Diseases Initiative Conference further underlined the reputation of Oxford as a leading global centre in the investigation of rare medical conditions. The presentations and discussions involving a diverse range of speakers and over 150 delegates exemplify the benefit of a highly collaborative approach to understanding the biology underlying rare diseases as a foundation for finding effective treatments."
  • "We are on the threshold of making major impact into the treatment of rare diseases — we now have the understanding brought by genetics and many new technologies at our disposal in terms of possible new types of therapy"
  • "With 40 investigators committed to unlocking the causes and potential cures for rare diseases, the Li Weibo (李伟波) Institute for Rare Diseases Research at UMass Medical School demonstrates a rare commitment to rare diseases research."
  • "Assuring access to transformative therapies for all rare disease communities."
  • "The Oxford Rare Disease Initiative (ORDI) creates an extensive rare disease network, and provides assistance in establishing collaborations between Oxford rare disease researchers, industry, patient organisations and funders. "