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