Rare diseases affect millions of people worldwide, but their low prevalence makes them unattractive for pharmaceutical development. Spain’s announcement of its co-sponsorship of a resolution on rare diseases at the upcoming World Health Assembly reflects the Ministry of Health’s initiative to increase its international presence. This resolution offers a unique opportunity to better align national and international policy priorities with equitable access to orphan drugs, including advanced therapies. In our new analysis, we explain the issues related with the innovation system for rare diseases, and its connection with national priorities in Spain. We also provide some proposals to align orphan drug R&D policies at national and international levels, directing it towards a more equitable and transparent system.
What Are Rare Diseases?
Rare diseases are conditions that affect a small percentage of the population, making them less profitable for investment by the pharmaceutical industry. Definitions vary by region, as there is no specific list of rare diseases (unlike neglected tropical diseases). Instead, they are defined based on prevalence in each region: conditions affecting less than 200,000 people in the United States, less than 50,000 people in Japan, or a maximum of 5 in 10,000 people in the European Union.
The Pharmaceutical Innovation Model for Rare Diseases: More Challenges Than Solutions
Given the lack of industry interest in developing orphan drugs, many countries have implemented public policies to incentivize innovation in rare diseases. While these policies have enabled significant progress, they have also highlighted systemic issues in the orphan drug innovation model:
- Unaffordable Prices: Orphan drugs are often launched at very high prices due to market exclusivity—a type of monopoly granted by countries that prevents generics, biosimilars, or other treatments for the same indication from entering the market.
- Monopoly Extensions: Orphan drugs can receive multiple designations for each indication, extending market exclusivity periods for decades. This is often achieved through the artificial subdivision of diseases into smaller categories to obtain more orphan designations.
- Neglect of Certain Diseases: While oncology treatments dominate orphan drug development, other rare diseases remain largely overlooked.
CAR-T Therapies: A Case Study on the Challenges of the Rare Disease Innovation System
CAR-T therapies have revolutionized the treatment of certain rare cancers. In fact, all CAR-T therapies approved by the FDA and EMA are designated as orphan drugs (except Breyanzi in the EU, where three designations were voluntarily withdrawn by the sponsor). They help illustrating the systemic issues caused by orphan drug incentives, including extended monopolies, unaffordable prices, and unequal global access.
According to FDA and EMA data, CAR-T therapies enjoy an average of 10.14 additional years of monopoly in the United States, which is 1.45 years longer on average than other orphan drugs. Furthermore, each CAR-T therapy has between 9 and 2 orphan designations, averaging 2.49 more designations than other orphan drugs. In the European Union, it is estimated (since the information is not publicly available) that CAR-T therapies benefit from 10.96 years of monopoly due to orphan drug incentives and have between 4 and 1 designations each. The prices for these therapies in the U.S. are around $400,000 per treatment.
Regarding global access to CAR-T therapies, a preliminary analysis of countries hosting clinical trials for commercial CAR-T therapies reveals an unequal landscape. Most trials are conducted in high-income regions, including the U.S., Canada, Europe, Japan, Australia, and China. While conducting trials does not guarantee treatment availability, it might give some insights into the geographic focus for future commercialization efforts.
Global and national implications of pharmaceutical policies
The development of CAR-T and other advanced therapies has become a key health and industrial policy priority in Spain, where an ecosystem for the development, production, and commercialization of affordable advanced therapies for the National Health System is taking shape.
In Spain, the list prices of commercial CAR-T therapies range between €360,000 and €320,000, although the actual net prices remain unknown because the Ministry of Health refuses to disclose the discounts negotiated with the industry. An exception to these prices is ARI-0001, developed by the Hospital Clínic of Barcelona, which costs €89,270 per treatment. This therapy is one of the best examples of Spain’s R&D model for advanced therapies, authorized through the exceptional Hospital Exemption procedure for cases of relapsed or refractory B-cell Acute Lymphoblastic Leukemia in adults, a type of cancer classified as rare.
The lack of transparency in setting net prices (after confidential discounts) poses an accountability issue nationally, as it prevents a clear understanding of public expenditure on these therapies. Additionally, it contributes to higher prices in other countries that use Spain’s list prices as a reference. Furthermore, the use of market exclusivity rules in the European Union increases the price of medicines used in Spain, impacting the sustainability of the healthcare system.
This shows how national pharmaceutical policies have international implications (and vice versa). To give another example, the EU’s orphan drug incentives can hinder Spain’s strategy for developing advanced therapies, as the current legislation prevents market entry for orphan drugs if another treatment for the same indication is already approved. That means that under the current legislation (and the proposed reforms being negotiated), ARI-0001 might not be able to be marketed in the European Union until Tecartus’s market exclusivity period ends (estimated in 2030), as both share the same indication.
In addition to expanding this analysis, our new publication includes a series of recommendations to ensure greater coherence in pharmaceutical policies, focusing on equity in access, increased transparency, and enhanced international collaboration. Our recommendations address three active processes in this area: the Resolution on Rare Diseases co-sponsored by Spain, the negotiation of European pharmaceutical legislation, and the development of advanced therapies within Spain’s public sector.
