Category Archives: ilS Speaker Series

ilS Speaker Series(SM): 2nd Edition Highlights on Orphan Drugs and their Access to Patients

By Anna Reyes, MSc, Consultant at Insights in Life Sciences (ilS).

ilS Speaker Series 2015The Second Edition of ilS Speaker SeriesSM titled “Orphan Drugs: How to Accelerate their Access to People Who Suffer from Rare Diseases?” was celebrated last Friday, March 27th, at the Rafael del Pino Auditorium in Madrid. Similarly to the First Edition, the event counted with the participation of industry representatives, health authorities, leading physicians and researchers and members from patients’ associations.

In the opening, Dr. Regina Revilla (President of the Spanish Association of Bio-Companies, ASEBIO) highlighted both the importance and impact of the Rare Diseases for the public National Health System (NHS) and made a call to all the health agents to commit themselves in collaborative efforts with patients. In the current situation, “rare diseases must be a priority in health policies”, Dr. Revilla said. Right after, Mr. Juan Carrión (President of the Spanish Federation of Rare Diseases, FEDER) stressed that the access to Orphan Drugs remains one of the biggest worries for patients. In his own words, “accelerating the access of orphan drugs means improving patients’ quality of life”, so it should be first priority for governments to do so without inequalities between regions.

Dr. Itziar Escudero, partner at ilS, gave a brief overview on rare diseases and shared some interesting numbers with the audience. A rare disease affects less than 5 out of 10,000 individuals. The 80% of cases are of genetic origin and they affect 3 million people in Spain. Although 6,000 to 8,000 rare diseases exist, medical and scientific knowledge is available only for the 30% of them. In Spain, the NHS finances 45 out of the 62 European Medicine Agency (EMA) approved orphan drugs and this year 1.7 M€ will be destined to the Strategy in Rare Diseases.

As Mr. Carrión, Mr. Justo Herranz, member of the Advisory Board of FEDER, pointed out the administrative issues, the unmet needs regarding access and the inequities across regions that Orphan Drugs are facing. The vast majority of rare diseases are chronic, disabling and have late diagnosis. A 27% of patients have received an inadequate treatment while a 30% suffer disease progression by the time diagnosis is revealed. The health system decentralization in Spain is detrimental to all patients suffering from Rare Diseases, given that assessment criteria for Orphan Drugs are strict and mandatory at regional and hospital level. Drug expenditure is the driving force for decision making regarding reimbursement and some penalties have been applied to health centers whose drug expenditure has exceeded budget. Mr. Herranz told the audience “this type of reality does not, by any means, give answers to the severe needs of patients”. FEDER is fighting for the establishment of Center Services of National Reference (CSUR), centers where patients coming from any region can be assisted accordingly (in-site or online) by the best specialists. The reality so far though, is that many centers are still unwilling to set up a CSUR for economic reasons and many hospitals are still opposed to the creation of clinical registers for Rare Diseases. However, Mr. Herranz was determined: “we can’t let ourselves the luxury of falling into hopelessness”.

The round table revealed an interesting, open and vibrant discussion about all the key aspects about the access to Orphan Drugs. From the R&D side, Dr. Palau highlighted that during 2009-2014, 328 R&D Spanish projects funded by the Health Institute Carlos III (ISCIII) and some other public grants have been carried out in the field of Rare Diseases. Although the current economic situation has forced the reduction of many of the resources, Spanish research is still out there and it is bearing its fruits. Some clinical trials are already ongoing for Orphan Drugs, as well as some studies for drug screening and gene or cellular therapy. Scientists are particularly interested in unveiling the genetic origin of these diseases and for that reason, 352 genes are under study. Besides, there are European Reference Networks (ERNs) for Rare Diseases and Spain will be taking part of them through CSUR centers, publicly financed by the government.

Dr. Blázquez indicated that European regulations in the field of Orphan Drugs count 15 years now and that the balance of the whole period has been positive: more than 1,400 drugs have obtained the Orphan Designation. Last year 15 new Orphan Drugs were approved and, currently, 27 are being evaluated. Moreover, at regulatory level, Orphan Drugs could benefit from market exclusivity, help in protocol elaboration, reduction of taxes to the European Medicines Agency (EMA) and support in R&D. It is important to mention that, in recent years, patients’ have gained their spot in regulatory commissions in Europe, while in Spain they are not a relevant stakeholder. Besides, Spain is standing up for the compassionate use when there is a clinical request from doctors, then some Orphan Drugs may be in clinical use for 4 or 5 months before regulatory approval.

Mr. Sánchez-Fierro stated that “there are elements of hope, but also elements of concern”. Barriers have lowered at European level, whereas Spanish internal barriers have somewhat strengthened. In Spain, drug assessments are conducted by a number of institutions (Spanish Agency of Medicines and Sanitary Products (AEMPS), health departments from autonomous communities, local hospitals, etc.) which, eventually, call patients’ rights into question from a practical point of view. Similarly, a Cohesion Fund once created is now kind of dissolving by many other funds that break the system’s wholeness. At this point, it is important to put ethics over economics and try to find the way out through objective and harmonized criteria across regions. Mr. Sánchez-Fierro also indicated that “ethics must be applied as well in clinical trials and compassionate uses by means of informed consent”. Patients must be always, at any point, informed about every action and risk being taken on them and the possibility of retracting in a language they can easily understand.

“Price negotiations within industry and Ministry of Health are public debates. Industries always pursue, as a priority, the return of the R&D investment as well as the company’s viability”, Mrs. Serrano explained. Only 3 out of 10 drugs cover R&D expenses. Additionally, in the field of Orphan Drugs, prevalence is really low so drug prices must be higher versus other drugs to return investment. Notably, the investment needed to develop an Orphan Drug exceeds the 1,200 M€ and many years of hard work on average; nevertheless, the return, if achieved, is only around 5-10%.

Ministry of Health’s price and reimbursement criteria for Orphan Drugs are the same as for the rest of innovative drugs. Among the most important criteria for drug reimbursement, we may find degree of innovation and therapeutic value of the drug, severity, duration and negative effects of the disease, cost-effectiveness and budget impact for the NHS. “Cost-effectiveness and budget impact criteria trigger all the issues this type of drugs present”, said Mrs. Martínez. Still, Orphan Drugs are reimbursed based on the answer they give to other important criteria such as severity and consequences of Rare Diseases, together with the huge impact they have on patients. At regional level, the cost of these products is really high due to the exclusivity of the Orphan Drug, which lowers the price flexibility, limiting payer’s options. There are no specific funds for Orphan Drugs currently in Spain. Although Orphan Drugs’ national reimbursement in Spain is remarkably high (80-90%), hospital managers handle budgets destined to cover all hospital treatments, not only Rare Diseases treatments. They have the last word regarding those decisions affecting the hospital’s budget overall and pharmacoeconomics plays an important role.

During the Q&A with the public, the role of hospital managers was brought up to discussion again. In conclusion, all contributions pointed that the responsibility for the access should be taken by the government, instead of health personnel. A single system without barriers between regions, for instance based in the recent national Therapeutical Positioning Reports (IPT), could help to avoid such drugs’ reassessments at regional or local levels and to lower hospitals’ budgetary pressure. In addition, strategies between biopharmaceutical companies and payers were proposed to accelerate Orphan Drugs’ accessibility to patients. These state alliances, defended by speakers and audience including Dr. Muñoz (Ex-President and Founder of Superior Council of Scientific investigations (CSIC)), might take place in the form of regulated pay per performance agreements, expenditure ceiling agreements, maximum expense per patient agreements or maximum global expense agreements. Because Rare Diseases are not only a pharmacoeconomic concern but a social and therapeutic one too, social responsibility from all health agents is needed in order to improve the current dynamics and eventually achieve a good equilibrium for all parts towards the future. Finally, speakers agreed on the need of an epigraph for Rare Diseases within the National Cohesion Fund of the Ministry of Health.



The impact of Rare Diseases in Spain

By Anna Reyes, MSc, Consultant at Insights in Life Sciences (ilS).

Rare Disease DayA 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

Globally, it is estimated that between 6,000 and 8,000 Rare Diseases exist.2 However, minimal medical and scientific knowledge is just available for the 30% of them.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:


1 Website European Commission. EC Regulation on Orphan Medicinal Products (04/03/15)
2 El País 17/02/2015
3 Webconsultas 04/03/2015 (04/03/15)
4 Website Centro de Referencia Estatal de Atención a Personas con Enfermedades Raras y sus Familias de Burgos (Creer) (04/03/15)
5 Website Federación Española de Enfermedades Raras (04/03/15)
6 Website Asociación Hemoglobinuria Paroxística Nocturna (04/03/15)
7 Website Organización Mundial de la Salud (04/03/15)
8 Website Medline Plus (04/03/15)
9 Website Instituto Nacional de Artritis y Enfermedades Musculoesqueléticas y de la Piel (04/03/15)
10 Website Federación Española de Fibrosis Quística (04/03/15)
11 Website Asociación Duchenne Parent Project España (04/03/15)12 Gaceta Médica 31/10/2013
12 Gaceta Médica 31/10/2013
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
14 Nuevos modelos de financiación pública en medicamentos huérfanos. Mercedes Martínez Vallejo.
15 El Global 23/02/2015
16 20/02/2015

ilS Speaker Series: Drug P&R Criteria in the UK and Spain

Barcelona, 7th of March.

ilS celebrated its first year launching its first ilS Speaker SeriesSM at their head quarters, in Barcelona.

The objective of the ilS Speaker SeriesSM was to generate debate and create knowledge. And the topic chosen for the event focused on a comparison between the P&R criteria used in the UK and Spain.

Dr. Pepi Hurtado, partner at ilS and expert in the UK Health System, explained to attendees the current changes in the National Health Service (NHS), and how decisions are taken in regards to the introduction of new drugs in the NHS. On the other side, Dr. Poveda, President of the Spanish Society of Hospital Pharmacy (SEFH), presented to the attendees the current P&R criterion in Spain, focusing on the need of a single and transparent P&R system for drugs should be implemented.

Attendees included representatives of the pharmaceutical industry and pharmacy hospital managers across the most relevant Spanish Hospitals. In addition Dr. Argimon, director of the Catalan Drug Evaluation Agency (AQuAS), together with Dr. Revilla, president of the Spanish Society of bio Companies (ASEBIO) attended the event.

For further information please have a look at:

To download the ilS Speaker Series presentation click here:

From left to right: Dr. Argimon (Director of AQuAS), Dr. Hurtado (partner at ilS, speaker at the even), Dr. Revilla (President of ASEBIO), Dr. Poveda (President of SEFH, speaker at the event), Miss Merhart (Life Sciences Advisor at UKTI, speaker at the event) and Dr. Escudero (partner at ilS, speaker at the event)