By Anna Reyes, MSc, Consultant at Insights in Life Sciences (ilS).
A Rare Disease is a disease which affects a limited number of the total population, defined in Europe as less than 5 in 10,000 citizens.1 The origin, in nearly eight out of ten cases, is genetic and they affect both children and grown-ups.2 In case the disease affects less than 1 in 50,000 people, we would be referring to it as an Ultra-Rare Disease.3
A 6 to 8% of the worldwide population is affected by such diseases, which translates into more than 3 million Spanish people, 27 million of Europeans and 25 million of North-Americans.3 If we estimate an average of 4 people per family, in Spain there are about 12 million people who daily live with a Rare Disease, either for directly suffering from them or for being closely related to a person who does.4
About 50 Rare Diseases affect several thousands of people in Spain, about 500 affect no more than a few hundreds and few thousands apply hardly to tens of people. Specifically in Spain, the Federación Española de Enfermedades Raras (FEDER)5 indicates that the five most common affections within the group of Rare Diseases are:
- Hemoglobinopathies (mainly Thalassemia and Drepanocitosis): They affect around 10,000 Spanish people. They are diseases which affect the survival or formation of the erythrocyte, altering the oxygen transport.1,2 Drepanocitosis can be treated with simple measures: plenty of liquid intake, healthy diet, folic acid supplements, analgesics, vaccines and antibiotics for preventing and treating infections. A severe thalassemia requires periodic blood transfusions. Multiple transfusions produce an iron over-load in several organs, alteration which also needs treatment. Thalassemias can be cured by means of bone marrow transplants, but these remain an expensive intervention that is not easily available in the vast majority of centers. Recently, gene therapy has succeeded in a patient with thalassemia.6
- Amyotrophic Lateral Sclerosis (ELA): It affects 6,000 Spanish people. It is a disease in which nervous cells get damaged or die, being unable to send messages to the muscles and leading to a final state of muscular debilitation and inability to move either the body or the limbs.8 The cure is still unknown. A drug named Riluzole helps to delay the symptoms, allowing the patients to live longer. Other measures of treatment would include the use of medications to control the spasticity, anticholinergics for those patients who present problems to shallow their own saliva, gavages to facilitate feeding, constant mechanical ventilation to breathe, physiotherapy and rehabilitation.8
- Scleroderma: It affects 5,000 Spanish people. The disease makes the connective tissue turn stiff and thick. It can also cause inflammation or pain in the muscles and articulations. Some types can affect the skin, making it stiff and tense. Other types affect the blood vessels and main organs such as the heart, lungs and kidneys.9 The disease has no cure yet, but its symptoms and caused damages can be diminished by vasodilators, analgesics, antiinflammatories, exercise for articulations, frequent use of sun screen, permanent oral hygiene, constant hydration, medication for intestinal regulation and antihypertensives9.
- Cystic Fibrosis: Affects between 4,000 and 5,000 Spanish people. It is a degenerative disease which affects mainly the lungs and the digestive system. Nowadays, the pathology has no cure. The treatment is based on getting an adequate nutrition, using drugs which fight against the respiratory inflammations and infections and doing respiratory physiotherapy exercises, exercises to strengthen the muscles of the thorax to prevent deformities and some sport. When the disease reaches an advanced stage, the possibility of performing a pulmonary and/or hepatic transplant exists.10
- Duchenne Muscular Dystrophy (DMD): Affects 3,000 Spanish people. It is a progressive disorder of the muscles that causes their function loss and thus, all those affected end up losing their independence. This progressive muscle feebleness leads to serious medical problems. Affected children need a wheelchair when they are barely 12 and the average life expectancy is 30 years.11 Although there is not a cure yet, some accepted treatments exist. These reduce the symptoms and improve quality of life: corticosteroids administration, adequate feeding, hydrotherapy, physiotherapy exercises and periodic evaluation of the muscular, respiratory and cardiac functions.11
In terms of expenditure, the direct economic impact of these diseases is high. At domestic level, the cost of the treatment for such an infrequent disease ranges from 500 to 700 euros per family per month.12 An epidemiologic observational study in 2012, with 593 Spanish patients suffering from 8 types of different Rare Diseases, determined that the greater cost of the families facing these diseases was informal care (care of the affected person) in the first place, followed in importance by the costs related to medical visits and drugs, respectively.13 At health system level, the cost is also really high, given that the investment needed to develop an Orphan Drug usually exceeds the 1,000 million euros and 12 years of work from the synthesis of the potential drug until its commercialization. Additionally, it has to be taken in mind that only 1 out of 100,000 investigated molecules reach commercialization in order to be available for those patients in need.3
The indirect economic impact is also highly relevant for those pathologies. The great majority of those patients affected require a certification of disability, which prevent them from working and therefore, from generating income and paying contributions to the National Health System. In the same way, caregivers also see their work and incomes compromised by the situation.
The current model of public funding for Orphan Drugs in Spain is a decentralized management model where the authorization decisions correspond to the Spanish Medicines and Sanitary Products Agency (AEMPS) and funding decisions fall on the Ministry of Health, Social Services and Equality (MSSSI). After the authorization and the funding, the price is fixed by the Interministerial Price Commission for Medicines (CIPM) and the Orphan Drug is put at health services’ disposal in the different autonomous communities, assuming each one of them has the responsibility of management and rational use.14
In Europe, the European Medicines Agency (EMA) has authorized 85 Orphan Drugs. In Spain, the AEMPS has authorized 69 of those active ingredients. However, only 47 products have been granted price and reimbursement and are currently marketed; the 22 remaining drugs are still pending the reimbursement decision by the CIPM. 15
Presently, those affected by a Rare Disease wait an average of 5 years in order to be correctly diagnosed, reaching the 10 years in 20% of the cases. This fact implies a series of negative and irreversible consequences in the majority of cases, which could have been avoided in addition to the disease worsening in 30% of the patients. Until this date, FEDER has registered more than 3,160 consultations of affected people without diagnostic.2 Among the causes for diagnostic delay, we find lack of adequate diagnostic tests, lack of coordination among professionals of primary and specialized attention and the barriers among autonomous communities in the case of Spain.
In order to solve this problem, FEDER is willing to start a program aimed at those people who are in doubt of suffering a Rare Disease and have no diagnosis yet. The objective is to create specialized laboratories across locations, where patients could go and run all the necessary tests required to diagnose or study the pathology. The offered services would include clinical testing, second medical opinion, genetic testing and neonatal screening, among others.16
ilS has decided to focus the Second Edition of its ilS Speaker SeriesSM (March 27th in Madrid, Spain) on this subject with a presentation entitled: “Orphan Drugs: How to Speed Up their Access to Patients with rare diseases?”.
See the agenda and register to the event: www.ilsintelligence.com/ils-speaker-series
1 Website European Commission. EC Regulation on Orphan Medicinal Products http://bit.ly/1Elvl4w (04/03/15)
2 El País 17/02/2015 http://bit.ly/1vVfpoA
3 Webconsultas 04/03/2015 http://bit.ly/1B70F4Y (04/03/15)
4 Website Centro de Referencia Estatal de Atención a Personas con Enfermedades Raras y sus Familias de Burgos (Creer) http://bit.ly/1DNMBMk (04/03/15)
5 Website Federación Española de Enfermedades Raras http://bit.ly/1C3HlIJ (04/03/15)
6 Website Asociación Hemoglobinuria Paroxística Nocturna http://bit.ly/1zJTICV (04/03/15)
7 Website Organización Mundial de la Salud http://bit.ly/1zYnlBN (04/03/15)
8 Website Medline Plus http://1.usa.gov/1iA006l (04/03/15)
9 Website Instituto Nacional de Artritis y Enfermedades Musculoesqueléticas y de la Piel http://1.usa.gov/1AJheQO (04/03/15)
10 Website Federación Española de Fibrosis Quística http://bit.ly/1sAyNCf (04/03/15)
11 Website Asociación Duchenne Parent Project España http://bit.ly/1wIawj7 (04/03/15)12 Gaceta Médica 31/10/2013 http://bit.ly/1zYnsgv
12 Gaceta Médica 31/10/2013 http://bit.ly/1zYnsgv
13 Los costes socioeconómicos y la calidad de vida relacionada con la salud en pacientes con enfermedades raras en España. Proyecto de IMSERSO Nº 167/10 http://bit.ly/1B1FzGh
14 Nuevos modelos de financiación pública en medicamentos huérfanos. Mercedes Martínez Vallejo. bit.ly/1M5OfNF
15 El Global 23/02/2015 http://bit.ly/1aLxiwo
16 Lainformacion.com 20/02/2015 http://bit.ly/1F9XDxH