How common are rare diseases and is enough being done to improve patient care?
Rare diseases are a set of conditions which affect a very small number of people when compared with more common conditions like diabetes or heart disease. There is no universal definition of rare diseases, and countries differ in the threshold they use to define a disease as ‘rare’.
Table1: Rare disease prevalence (cases per population) across various countries.
New rare diseases are being discovered all the time but overall, there are about 5,000-8,000 rare diseases. Collectively, rare diseases affect approximately 6-10% of the population and 3-4% of childbirths. 80% of rare diseases have a genetic influence, and the rest may occur due to viral or bacterial infections, allergies, and other environmental causes. Globally, it is estimated that approximately 350 million people suffer from rare diseases of which around 8.6% are from Europe.
Rare diseases exhibit substantial multiplicity in aetiology and clinical presentation, and most of them have severe effects on life expectancy, and physical and mental abilities. Many rare disease patients experience barriers in access to patient care, and fewer than 10% receive disease-specific treatment. Delayed diagnoses, limited access to resources, and absence of specific therapies often preclude patients from receiving proper, timely care. When patients are diagnosed, many are unable to access resources such as centers of expertise, coordinated care, patient support systems, and effective treatment. Therefore, research into the natural history and underlying pathophysiological mechanisms of rare diseases is necessary to develop a foundation for discovering targeted medications.
Approximately 7% of people will be affected by rare diseases at some point in their lives, showing that rare diseases aren’t so rare at all. Yet, over the years, their classification as rare has led them to often be ignored, with pharmaceutical companies and public health systems concentrating their efforts on developing treatments for diseases typically viewed as being more common.
Recent strides in medical research have helped to make it possible for scientists to target rare diseases, and advocacy groups have been urging researchers in that direction. Sensing that the era of “blockbuster” drugs is coming to an end, pharmaceutical companies have also become more willing to direct their R&D departments to look at orphan drugs for new possibilities. This is why they have become a growing market – one that is, in fact, growing even faster than the market for traditional drugs, and which has some 400 drugs currently in development. Despite these advances in drug development, many rare diseases lack any treatment options.
There are a number of potential ways that have been considered to address this, including bringing in government-sponsored drug development, elevating the patient voice, and partnering in the development of programs to address the needs of patients with rare diseases.
Rare diseases communally exert a global public health burden in the severity of their manifestations and the total number of people they afflict. Many rare disease patients experience serious market access issues that hinder the diagnosis and treatment of their disease conditions. Driven by these challenges, the rare disease patient community has played a vital role in elevating the patient voice and organizing legislation to support the development of programs that address the needs of patients with rare diseases.
The US Orphan Drug Act of 1983 served as a breakthrough, providing a roadmap for other countries to introduce and implement orphan drug legislation. More recently, the European Union (EU) has gone further to encourage the widespread adoption and execution of rare disease plans or strategies designed to more adequately address the comprehensive needs of patients with rare diseases. Despite these legislative efforts and the growing contributions of patient advocacy groups, gaps still exist across the policy landscape for several countries.
Safiyya Dharssi and her colleagues once reviewed the rare disease policy landscape across eleven countries (some emerging markets, some developed) – Germany, France, the United Kingdom, Canada, Bulgaria, Turkey, Argentina, Mexico, Brazil, China, and Taiwan. Their study explored the rare disease legislation, associated policies, regulation, programs, status, and implementation of policy for each country in the context of key patient needs across five dimensions: improving the coordination of care, diagnostic resources, access to treatments, patient awareness and support, and promoting innovative research.
Their findings emphasize the continuing role of the patient community in driving the establishment and adoption of legislation and programs to improve rare disease care. Additionally, they found that while national rare disease plans provide important guidance for improving care, implementation of plans is uneven across countries. As a final point, they accentuated the need for more research to demonstrate the effect of specific elements of rare disease plans on patient outcomes.
Table 2: Orphan drug legislation timeline
1. Shire in association with Hereditary Angioedema International (HAEi) and the HAE Association (HAEA), developed the HAE patient identification and diagnosis program which helps to recognize the gaps in physician, patient and family member knowledge, and also to develop a core set of materials to educate them.
Collective materials, which consist of information regarding the HAE disease and its diagnostic tests, were designed for all three key participants. But, taking the comfort of the patients into consideration, materials related to the patient were developed by patients to assure a better approach. Forty one member groups worldwide were identified and trained by the HAEi and HAEA to utilize the materials designed. Webinars and regional workshops were organized to enable awareness in the countries where there were no patient organizations identified, .
HAEi, HAEA, and Shire have broadened the awareness of HAE and improved diagnostic training for healthcare professionals internationally by strategically working together. There was a very encouraging response from the HAE community with an increase in both the number of patients and members of country organizations. In the United States alone, 340 patients participated in the campaign, and over 700 new members joined the campaign.
2. Haemophilia is a lifelong, chronic condition if left untreated or undertreated, and causes bleeding, including into joints which causes progressive joint damage. The Swedish Orphan Biovitrum (SOBI) came to realize that the design of packaging and dosing syringes was not always meeting the needs of people with haemophilia, sometimes being bulky and difficult to manage. Before filing the marketing authorization application in Europe, SOBI started exploring if more user-friendly packaging and administration could make life easier for haemophiliacs. They were asked to record video diaries of their treatment experiences, and interviews were conducted with them to better understand the topics they had raised.
The inputs were used to prepare potential new designs for the packaging and syringes. These were shared with the haemophilia community to explore if these designs would better meet their needs. SOBI thus learned that size was the most important element, and the resulting package was more compact, and easier to travel with and store.
Haemophiliacs might have impaired grip function due to joint damage. So, an innovative syringe plunger rod with horizontal ribs and an extra center grip with a soft top was designed. This increases friction and gives equal grip, even if it is not pushed exactly squarely.
3. Compassionate Use Programs for Rare Diseases:
Because of highly engaged patients and caregivers connected to advocacy groups, since 2010, the number of compassionate use requests has risen by nearly 25% and a majority are from rare disease patient populations. Many pharmaceutical companies are facilitating access to such drugs. Lately, Genzyme Corporation has donated imiglucerase to hundreds of severely affected patients with Gaucher’s disease in three large-scale international CUP. These kind of efforts by pharma majors to improve early access to life-threatening disease drugs is a good initiative.
All parties were able to bring individual strengths and knowledge to the project for the benefit of patients by working together. The result was not just more information but also a framework for global and regional organizations to ensure that member groups are able to execute effectively. This cooperation between industry and advocates provides an approach that can be replicated across other disease areas. This will create opportunities for continued validation and refinement of future approaches.
Rare diseases are a public health priority. Hence, awareness should be raised among policymakers, healthcare professionals, and the general public. Patients and their wider communities should be empowered, enabling better disease management, and for patients to further influence the decisions that affect them. Continued research and development should be promoted, building political commitment to drive research, innovation and policies for rare diseases, and increasing collaborative research efforts to enhance scientific understanding of all rare diseases. Sustainable access to diagnosis, treatment, and care should be ensured, improving the workforce and infrastructure to treat rare diseases, and developing and strengthening legislation that enhances access to orphan drugs.