Biotechnology is providing answers to rare diseases in areas with unmet clinical needs such as diagnosis and treatment, through advanced therapies, biomarkers and the development of new therapeutic options.

The World Health Organization (WHO) estimates that there are more than 7,000 defined rare diseases affecting up to seven percent of the world’s population. These are characterized by a low prevalence in the population: they affect less than five out of every 10,000 people. The Spanish Federation of Rare Diseases (Feder) estimates that, in Spain, around three million people live with rare diseases or are in search of a diagnosis.

The lack of information and research on rare diseases is one of the main barriers faced by those affected. Feder indicates that only 20% of the more than 6,313 rare diseases identified in Europe are currently being researched. In addition, there is the problem derived from the different ways to achieve a diagnosis. In this regard, for example, neonatal screening, the application of which varies both at European level (currently covering a minimum of seven pathologies) and at state level (in some autonomous communities there are more than 40).

Other diagnostic methods, such as genetic testing, are added to this screening. Recently, the Ministry of Health presented its new Catalog of Genetic Tests, which represents an important step forward in terms of early access to diagnosis, together with the recent announcement of the recognition of the specialty of genetics.

Despite these advances, rare diseases continue to be the great forgotten ones. Forty-three percent of people suffering from a rare disease have no treatment and, if they do, it is inadequate. Feder denounces that more than 30% of people living with rare diseases have experienced a delay in diagnosis, which has led to an aggravation of their disease. In addition, 29% do not receive any kind of support or treatment and up to 18% would not have received adequate treatment for their disease.

Biotechnology is radically transforming the approach to rare diseases

In the face of this worrying scenario, biotechnology is offering answers in areas with unresolved clinical needs such as diagnosis and treatment. Genetic engineering, especially in the field of pharmacology, is achieving significant advances against rare diseases such as Fabry, Pompe or Gaucher diseases. In recent years, advanced therapies are providing answers to some rare diseases, such as tissue therapy and butterfly skin disease. In this regard, it is worth noting

Only six percent of rare diseases have medicines and access to them is unequal, so guaranteeing access and equity, reducing access times and encouraging the development and research of new treatments is fundamental. Biotechnology has positioned itself as a key player in this challenge and is laying the foundations for the future of medicine. In recent decades, biotechnology has transformed the discovery of new drugs, with more than 300 approved biotechnology drugs for around 250 indications, and a thousand molecules in different phases of research around the world to find new therapeutic active ingredients or find new applications for existing ones.

“The good news is that there is more awareness and more research compared to a few years ago, but unfortunately for most diseases there is still no treatment or advanced development projects. There is still a lot to do,” says Marc Martinell, CEO of Minoryx Therapecutics, a biotech company focused on finding new treatments for serious rare diseases with a focus on pediatric diseases.

Research, cornerstone in the fight against rare diseases

Feder emphasizes that Spain “has always been a pioneer in rare diseases, being one of the first to promote its own Strategy or leading the proposed UN Resolution. However, we find big differences with other European countries in key aspects such as investment in research, the different neonatal screening tests for access to early diagnosis or access to orphan drugs”.

The International Rare Diseases Research Consortium (IRDiRC) lists the main research challenges facing rare diseases. Broadly speaking, these include promoting the development of new therapies for rare diseases in Spain (the international objective has been set to have 1,000 new therapies globally by 2027), and supporting the development of diagnostics (the goal has been set for 2027 that any person affected by a rare disease should be diagnosed in less than a year).

Research is fundamental to achieve progress in the treatment of rare diseases. In the case of our country, most of the funding for rare diseases is focused and centralized, from an operational point of view, through the Center for Biomedical Research in Rare Diseases Network (CIBERER). This is made up of a team of more than 700 professionals and integrates 56 research groups, 20 linked clinical groups, belonging to institutions of a diverse nature.

“Research in low prevalence diseases has experienced a remarkable growth in recent years, although, of course, there are currently many unmet needs, given the intrinsic characteristics of this group of pathologies, such as: high number of diseases, geographical dispersion, less interest from the pharmaceutical industry, lack of specialized training, scarcity of resources, etc.”, explains Beatriz Gómez González, Manager of the Scientific Activity of the CIBERER.

“The challenges in Spain, which of course coincide with the objectives of the IRDiRC, are to achieve higher and earlier diagnosis rates, faster drug development at reduced costs, improved patient care and the empowerment of all stakeholders,” explains Beatriz Gómez, who stresses that “the low prevalence of the diseases makes it difficult to set up clinical trials, as well as to attract funds from the private sector for the development of the last phases of clinical trials and commercialization”.

The CIBERER highlights the crucial role played by biobanks in research into rare diseases. They stress that the availability of biological samples in the case of rare diseases is very limited. “Biobanks make it possible to store samples for national and international research, which makes it possible to obtain more solid and conclusive research results”, which is why in 2010 they set up the CIBERER Biobank, a public, non-profit biobank that centralizes the reception of pediatric and adult samples of high biological value for research into rare diseases.

CIBERER groups research directly or indirectly in more than 2,000 rare diseases or groups of rare diseases, from different approaches, whether molecular, diagnostic or therapeutic. Among the achievements that can be highlighted, for example, in the diagnostic field, it can be highlighted that the center’s researchers have described more than 120 new genes associated with rare diseases in the last decade. Furthermore, in the field of new therapies, the center has contributed to the designation of 28 orphan drugs in Europe or the United States and has directly sponsored 15 of these drugs.

Orphan drugs: challenge in the fight against rare diseases

Orphan drugs are drugs developed specifically to diagnose, prevent or treat rare diseases. Due to their low prevalence, they are often not economically attractive for pharmaceutical companies to develop and market treatments under normal market conditions.

The designation “orphan” refers to the lack of interest on the part of pharmaceutical companies to develop and market treatments for conditions that are rare because the return on investment is uncertain or unlikely. The importance of orphan drugs lies in the fact that they provide needed treatment options for patients who might otherwise have no hope of treatment due to the rarity of their condition. These drugs contribute to improving the quality of life and, in some cases, prolonging the survival of patients with rare diseases.

Asphalion, an International Scientific and Regulatory Affairs consultancy, has expert teams dedicated to analyzing the context of each therapeutic product intended for the treatment of rare diseases. They provide advice on the options available to obtain Orphan Drug Designation (ODD) and manage the entire process leading up to orphan drug designation.

“Orphan drug designation is a special status granted by the FDA or the European Medicines Agency (EMA) to drugs or substances that are intended for the diagnosis, prevention or treatment of rare diseases. Orphan drug designation is requested on a voluntary basis and free of charge, as it allows pharmaceutical companies to benefit from the benefits and incentives contemplated in the regulation to develop treatments for these rare diseases, and without which the marketing of these drugs would most likely not generate sufficient income to justify the necessary investment”, explain Asphalion, which stresses that “orphan designation does not establish that the drug is effective or safe, but it does indicate that the drug meets the definition of orphan established in the regulation”.

The current problems faced by orphan drugs in Europe and Spain are multifaceted and complex. In the case of Europe, Asphalion identifies obstacles such as high cost and market access since “marketing authorization does not guarantee access to patients, as each EU country has its own reimbursement and health technology assessment (HTA) system, which can result in delays”. They add other problems such as the lack of clinical evidence (clinical trials of these drugs usually have a small number of participants), inequality in access and the sustainability of healthcare systems that “are under pressure to finance expensive orphan treatments, which raises questions about sustainability and equity in the allocation of resources”.

In the specific case of Spain, they allude to the fact that the process of financing an orphan drug is long and complex, the challenge posed by health technology assessments for these drugs given the scarcity of data, limited budgets and the lack of knowledge and expertise in rare diseases.

“In response to these challenges, initiatives are underway at the EU and national levels to improve access to orphan drugs, including collaboration on the evaluation of HTAs, initiatives to improve pricing and reimbursement systems, and efforts to encourage research and development in the field of rare diseases,” Asphalion argues.

“Obtaining ODD simplifies the already complex process of developing drugs for rare diseases. By providing support in this regard, our aim is to maximize the chances that the products will be approved and thus become therapeutic options for unmet medical needs,” they conclude.

Original news: La biotecnología, clave ante el desafío global que plantea el abordaje de las enfermedades raras- AseBio (29/02/2024).

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