Biotechnology emerges as a key player in the fight against rare diseases

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

Only 20% of the over 6,313 rare diseases identified in Europe are currently under investigation. The problem is compounded by the different pathways to achieve a diagnosis, such as neonatal screenings, the application of which varies both at the European level (currently covering a minimum of seven pathologies) and at the state level (some autonomous communities exceed 40). In addition to these screenings, other diagnostic methods such as genetic testing are used. Recently, the Ministry of Health has presented its new Catalog of Genetic Tests, representing a significant step in terms of early access to diagnosis, along with the recent announcement of the recognition of the genetics specialty.

43% of people with a rare disease have no treatment available, and if they do, it may not be adequate. Feder reports that over 30% of people living with rare diseases have experienced delays in diagnosis, resulting in worsening of their condition. Furthermore, 29% do not receive any support or treatment, and up to 18% may not have received appropriate treatment for their disease.
Biotechnology radically transforms the approach to rare diseases.

In response to this concerning scenario, biotechnology is providing answers in areas with unmet clinical needs such as diagnosis and treatment. Genetic engineering, particularly in the field of pharmacology, is achieving significant breakthroughs. In recent years, advanced therapies have been providing solutions, such as tissue therapy and butterfly skin disease.

In the last few decades, biotechnology has revolutionized the discovery of new drugs, with over 300 biotechnological medicines approved for around 250 indications, and thousands of molecules in various stages of research worldwide, aiming to find new therapeutic active principles or discover new applications for existing ones.

"The good news is that there is more awareness and research compared to a few years ago, but unfortunately, for most diseases, there are still no treatments or advanced development projects. There is still much to be done," Marc Martinell, CEO of Minoryx Therapeutics, a biotechnology company focused on finding new treatments for serious rare diseases with a focus on pediatric diseases, declares.

Currently, in the European Union, efforts are underway to obtain marketing approval for leriglitazone (Nezglyal) for the treatment of X-linked adrenoleukodystrophy (X-ALD). "In the United States, we are conducting a phase 3 trial in agreement with the Food and Drug Administration (FDA). For a large part of the population with this disease, leriglitazone could be the first drug to reach the market," he argues.

"We prioritize diseases with a pediatric component. The cerebral form of X-ALD (cALD) affects both children and adults and is lethal within three or four years," he points out. Minoryx emphasizes the urgent need to better understand rare diseases in order to develop treatments, reduce diagnosis times, and maintain long-term efforts and investments "to successfully bring drugs to approval," Martinell concludes.

Research, cornerstone in the fight against rare diseases

Feder highlights that Spain "has always been a pioneer in rare diseases, being one of the first countries to promote its own Strategy or leading the proposal of the UN Resolution. However, significant differences are found with other European countries in key aspects such as investment in research, the various neonatal screening tests for early diagnosis access, or the access to orphan drugs."

The International Rare Diseases Research Consortium (IRDiRC) outlines the main research challenges that rare diseases must face. Broadly speaking, they emphasize promoting the development of new therapies for rare diseases in Spain (the international goal is to have 1,000 new therapies globally by 2027) and supporting the development of diagnostics (the goal for 2027 is to diagnose anyone affected by a rare disease in less than a year).

In Spain, most of the funding allocated to rare diseases is focused and centralized operationally through the Biomedical Research Networking Center for Rare Diseases (CIBERER). This comprises a human team of over 700 professionals and integrates 56 research groups, 20 linked clinical groups, belonging to institutions of diverse nature.

"The research in low prevalence diseases has experienced significant growth in recent years, although, of course, there are currently many unmet needs," explains Beatriz Gómez González, Manager of Scientific Activity at CIBERER.

"The challenges in Spain, of course, align with the objectives of IRDiRC, which include achieving higher and earlier diagnosis rates, accelerating drug development at reduced costs, improving patient care, and empowering all stakeholders," states Beatriz Gómez.

The CIBERER groups directly or indirectly investigate over 2,000 rare diseases or groups of rare diseases, from various approaches, whether molecular, diagnostic, or therapeutic. Among the achievements, for example, in the diagnostic field, it can be highlighted that researchers at the center have described over 120 new genes associated with rare diseases in the last decade. Additionally, 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: a challenge in the fight against rare diseases

Orphan drugs are those developed specifically to diagnose, prevent, or treat rare diseases. Due to their low prevalence, they often are not economically attractive for pharmaceutical companies to develop and commercialize treatments under normal market conditions. A process not without obstacles and barriers for companies.

Asphalion, a consultancy specializing in International Scientific and Regulatory Affairs, has expert teams dedicated to analyzing the context of each therapeutic product intended for the treatment of rare diseases. "The designation as an orphan drug is voluntarily and cost-free since pharmaceutical companies can benefit from incentives and benefits provided in the regulation to develop treatments for these rare diseases, and without which the commercialization of such drugs would likely not generate enough revenue to justify the necessary investment," explain those at Asphalion, emphasizing that "the orphan designation does not establish that the drug is effective or safe, but it does indicate that the drug meets the orphan drug definition established in the regulation."

The current issue facing orphan drugs in Europe and Spain is multifaceted and complex. In the case of Spain, they refer to the fact that the funding process for an orphan drug is long and complex, the challenge posed by health technology assessments for these drugs due to the scarcity of data, limited budgets, and lack of knowledge and expertise in rare diseases.

"In response to these challenges, initiatives are being carried out at both EU and national levels to improve access to orphan drugs, including collaboration in HTA evaluations, initiatives to improve pricing and reimbursement systems, and efforts to promote research and development in the field of rare diseases," argue those at Asphalion.

"The acquisition of ODD streamlines the drug development process for rare diseases, which is already very complex in itself. By providing support in this regard, our aim is to maximize the chances of products being approved and, therefore, becoming therapeutic options for unmet medical needs," they conclude.