Rare diseases are a general term for a large class of diseases scattered in various disease systems, characterized by their low incidence and uncommon nature (The Lancet, 2020; The Lancet Neurology, 2022). These diseases are typically chronic and serious, often posing a significant threat to life (Chung et al., 2022; Rare diseases, 2022). Rare diseases are defined differently across countries (Richter et al., 2015; Adachi et al., 2023). Currently, the most widely adopted international approach for defining rare diseases involves establishing a threshold based on incidence rates or the number of cases. Diseases occurring below this threshold are classified as “rare” (Nguengang et al., 2020). In China, the current criteria specify an incidence rate of less than 1/10,000 among newborns, a prevalence rate of less than 1/10,000, or an affected population of less than 140,000 (Lu and Han, 2022).

Rare diseases have increasingly been recognized as a public health priority in China. On 11 May 2018, the National Health Commission, Ministry of Science and Technology, Ministry of Industry and Information Technology, National Medical Products Administration, and National Administration of Traditional Chinese Medicine jointly published China’s First List of Rare Diseases, which included 121 rare diseases (He et al., 2018). Subsequently on 18 September 2023, these five departments, along with the Logistics Department of the Central Military Commission, released the Second List of Rare Diseases, adding 86 diseases (Tang et al., 2023). Thus far, a total of 207 rare diseases have been included in the catalog management in China. The diseases listed in the catalog receive priority support from national medical insurance, local security initiatives, and incentives for drug research and development (Liu M. et al., 2024; Zhao et al., 2023).

Rare disease drugs are used for the diagnosis, prevention and treatment of rare diseases (Tambuyzer et al., 2020; Chen et al., 2024; Barrett et al., 2023). Due to the vast number of rare diseases, the smaller patient populations, limited market demand, and high research and development costs, fewer pharmaceutical companies focus on developing drugs for rare disease, leading to they are also called orphan drugs (Puig-Junoy and Campillo-Artero, 2019; Zhang et al., 2019). Multiple guidelines and consensuses have provided valuable insights into standardizing treatments for rare diseases (Burgos et al., 2024; Chen et al., 2021; de Graeff et al., 2019). Nevertheless, there remains a lack of clear policy regarding orphan drug qualification criteria as well as a mature list. Most existing studies focus on the marketing of orphan drugs, their efficacy, and comparative analyses between different regions (Giannuzzi et al., 2017; Gorini et al., 2022; Heard et al., 2020; Yang et al., 2019; Zhi et al., 2023; Liu et al., 2023; Liu Qingyang et al., 2024), but data on downstream drug supply and utilization are lacking. In particular, once relatively common drugs are excluded, the allocation of specific drugs can better reflect the effectiveness of local orphan drug supply systems. Therefore, this study aims to review the specific therapeutic drugs listed in the first and second rare disease catalog in China and analyze actual purchasing data from one eastern province. Our findings will provide a deeper understanding of local allocation and use of rare disease drugs, and offer insights for improving the capacity for treatment of rare diseases.

Since 2018, China has implemented a catalog management system for rare diseases, publishing two lists covering a total of 207 rare diseases. Similarly, Japan and South Korea have also adopted catalog-based management for rare diseases, confirming 338 and 1,147 rare diseases respectively (Feng et al., 2021; Yang et al., 2022). However, it is important to note that these catalogs cover only a fraction of the over 7,000 known rare diseases globally (Haendel et al., 2020). The groups of rare disease patients not included in these directories also warrant attention.

There have been several reports on the accessibility of orphan drugs in China, which indicate that the diagnostic level of rare diseases, the approval speed of orphan drugs, and the coverage of orphan drug improved rapidly after the implementation of a catalog-based management system (Kang et al., 2019; Qiao et al., 2022). Our study supports these findings, indicating a consistent annual increase in the number of specific therapeutic drugs, with several drugs experiencing explosive growth in procurement volume.

The availability of a drug on the market does not guarantee its accessibility for use. In Shandong Province, only 80% of the specific drugs listed in China are accessible, and there are currently 8 drugs in short supply. When considering epidemiological data, at least five diseases sufferers a lack of specific drugs available for treatment in the area. Among the diseases for which drugs are available in Shandong Province, the distribution rate of 16 drugs falls below 80%. Further investigation is warranted to identify issues in the production and distribution of these drugs, and concerted efforts are needed to enhance their availability.

The number of drugs has been increasing annually, but the total procurement expenditure has been decreasing. This trend is likely linked to the national medical insurance policy. Since 2015, China has embarked on a process to negotiate the inclusion of drugs in the national health insurance drug list. This process relies on price negotiations and strategic purchasing mechanisms to incorporate drugs into basic medical insurance coverage (Zhao et al., 2023; Tambuyzer et al., 2020; Yi et al., 2023; Tang et al., 2020). Research indicates that negotiated drug prices have been reduced by an average of over 60% (Chen, 2021). By 2022, 29 rare disease drugs had been included in the national medical insurance through such negotiations (Bi et al., 2023). Notable examples include the price reduction of Nusinersen Sodium Injection from 699,700 RMB to 33,180 RMB, Temozolomide Capsules from 19,675.8 RMB to 246.5 RMB, and Agalsidase Beta from 37,800 RMB to 34,000 RMB. Additionally, various regions have introduced supplementary medical insurance to further alleviate patients’ financial burdens. In Shandong Province, drugs for treating Gaucher Disease, Pompe Disease, and Fabry Disease have been included in the major disease medical insurance coverage (Liu M. et al., 2024).

There is a significant disparity in the quantity and procurement amounts of specific drugs to rare diseases across different regions, which may be attributed to the uneven distribution of medical resources (Qin et al., 2024; Fan et al., 2024). Provincial capital cities, usually characterized by robust economic development, significant political status, and abundant medical resources, tend to have a greater availability of rare disease medications. The findings suggest that while encouraging patients with rare diseases to seek treatment in higher-level medical institutions, regional diagnostic and therapeutic cooperation network for rare diseases could effectively optimize the allocation of medical resources.

Our study innovatively compiled a comprehensive catalogue of specific therapeutic drugs for rare diseases through a meticulous analysis of the first and second lists of rare diseases in China. This catalogue serves as a fundamental resource, enabling medical staff to rapidly grasp the corresponding therapeutic drugs for rare diseases. The analysis of the purchasing data regarding these drugs fills a significant void in the research on downstream drug supply and utilization. Moreover, it provides direct evidence for the expansion of drug coverage and the decrease in costs under the impact of policies. Additionally, regional disparities in the accessibility of rare disease drugs warrant attention.

However, it should be acknowledged that there are certain limitations. Firstly, the study proposed a definition of specific therapeutic drugs for rare diseases without an authoritative standard. Although two researchers independently conducted searches for the included drugs, the rarity and uncommon nature of rare diseases may have resulted in some drugs being overlooked. Secondly, the study did not take into account the timing of drug market entry, which may lead to some drugs purchase quantity is zero may be because the drug is not yet listed at the time. Additionally, the procurement data utilized does not directly equate to usage data. However, considering that orphan drugs are generally high-priced and low-usage and medical institutions typically do not maintain routine stockpiles, we believe that purchasing data can reflect the drug use to some extent.

In conclusion, this study has compiled a catalogue of specific therapeutic drugs for rare diseases by analyzing the first and second lists of rare disease. The analysis of procurement data in Shandong Province reveals a rapid increase in the variety of drugs procured in recent years, accompanied by explosive growth in the volume of multiple drug procurements. While 80% of specific therapeutic drugs are available locally, there is a need to further enhance drug supply capacity, particularly for drugs that are in short supply or have low delivery rates. Additionally, significant disparities exist in drug purchase amounts across different prefecture-level cities.