Rare disease research is undergoing a gradual shift from a primary focus on single-disease mechanisms and drug development toward a more comprehensive agenda encompassing healthcare systems, policy frameworks, and patient engagement. The themed issue of Intractable & Rare Diseases Research, entitled "Rare Diseases and Orphan Drugs in China: From System Building to Global Engagement," systematically presents China's recent efforts in building governance structures for rare diseases, strengthening clinical collaboration networks, increasing the use of real-world data, and fostering multi-stakeholder participation. Emerging within the context of a large population and pronounced regional disparities, the Chinese experience offers new analytical perspectives and practical reference points for global rare disease research. It also contributes to an ongoing paradigm shift—from isolated, single-disease breakthroughs toward the development of sustainable, system-level capacity.

Rare diseases represent a significant public health challenge in China, affecting an estimated 20 million individuals. Despite incremental policy improvements over the past decade, including the publication of two National Rare Disease Lists, an increasing number of available treatments, and the inclusion of some therapies in the Nationally Reimbursed Drug List (NRDL), patients continue to face systemic challenges in diagnosis, treatment access, and sustainable protection. That said, China has very limited rare disease research & development (R&D) and industrial development, so the market potential is far from being tapped. This policy review argues that the lack of a national legal definition for rare diseases and orphan drugs, an unsustainable payment mechanism for high-value innovative therapies, and insufficient incentives for domestic research and development have collectively hindered the creation of a sustainable rare disease ecosystem. Drawing on an analysis of patient registry data, policy documents, and proposals from China's National People's Congress (NPC) sessions, we demonstrate a growing societal consensus on the need for comprehensive national legislation on rare diseases, which is not only a moral imperative to safeguard the rights of patients but also a strategic necessity for a national population strategy and biomedical industrial development. We consider systemic rare disease legislation in China to be imperative, and now is the optimal time to promote rare disease legislation in China. We propose nine key initiatives, including establishment of a working committee on national legislation, creating a standardized definition of rare diseases and orphan drugs, creating a dedicated national rare disease fund, and robust R&D incentives.

The development, importation, and reimbursement of drugs and medical devices for rare diseases have become critical issues within China's healthcare system. Since 2018, China has issued two national Rare Disease Lists, covering 207 diseases. As of December 2025, 223 drugs for rare diseases have been marketed domestically, with 136 (61.0%) included in the national list for reimbursement by basic medical insurance scheme. Advances have also been made in diagnostic technologies and treatment equipment. This article also examines the issues with and factors influencing the pharmacoeconomic evaluation of rare disease therapies. Additionally, over 100 registered patient organizations contribute substantially to care, education, research, and advocacy. China has piloted multi-level healthcare security system, including national and local healthcare security systems. The introduction of a list of innovative drugs covered by commercial insurance in 2025 further supplements this system. These measures have collectively expanded reimbursement coverage. Despite progress in drug development, insurance coverage, and evaluation of drugs in terms of health economics, continued efforts are needed to enhance treatment accessibility and equity. Key measures include putting forward rare disease legislation, promoting research on health technology assessment, improving health utility measurement, encouraging domestic orphan drug development, and strengthening international collaboration. China's experience offers valuable insights for global rare disease prevention and treatment initiatives.

To ascertain the status and propose optimization strategies for rare disease drugs (RDDs) value assessment in the scenario of the National Reimbursement Drug List (NRDL) dynamic adjustment in China, we conducted a narrative policy review that synthesized published literature and policy documents, supplemented by a secondary descriptive statistical analysis of publicly available 2022–2024 year NRDL negotiation data to contextualize recent reimbursement practices for rare disease drugs in China. This study found that value assessment of RDDs largely aligned with the traditional framework, encompassing five key dimensions: safety, efficacy, economic evaluation, innovation, and equity. Considering disease severity and the competitive landscape, innovative RDDs tend to receive higher clinical value ratings, higher willingness-to-pay thresholds, and broader policy support across the healthcare system. Between 2022 and 2024, a total of 60 RDDs applied for NRDL inclusion, with 43% successfully reimbursed. Most applicants were either original research drugs already approved overseas or modified new drugs launched domestically and abroad. Notably, 42% of the drugs had achieved global first launches before 2015, thereby accumulating extensive clinical evidence, and 58% submitted randomized controlled trial (RCT) data. The proportion of drugs supported by RCT evidence in the reimbursed group was significantly higher than the figure in the non-reimbursed group, whereas the proportion of drugs with pediatric indications were relatively lower in the reimbursed group. No significant differences were observed in other value assessment dimensions between successful and unsuccessful applicants. It is recommended that China develop detailed health technology assessment (HTA) guidelines and real-world evidence (RWE) guidance tailored for RDDs, facilitating the generation of high-quality evidence and decreasing decision-making risks associated with the value assessment of innovative RDDs.

Foods for special medical purposes (FSMPs) is a type of products that provides targeted nutritional support for specific diseases or physiological conditions. Compared with conventional dietary therapy, FSMPs are more targeted, safer, and applicable in clinic. When FSMPs are used to treat rare diseases, their core principle is to bypass or alleviate metabolic disorders. With the increasing recognition of clinical treatment effectiveness and the growing demand from patients, the types and market scale of commercial rare disease FSMPs continue to expand. However, there are currently no article summarized and analyzed the characteristics of diverse commercial products. Based on this, this review collected and collated the vast majority of commercial rare disease FSMPs in the global market, and summarized the characteristics of these products by categorizing them into protein substitutes, nutritional modules, ketogenic diets (KDs), and special low protein foods (SLPFs). Following the comprehensive analysis of the global commercial rare disease FSMPs landscape, this review shifted focus to China and provided suggestions from product diversity, technological innovation, and policy optimization. It aims to offer available suggestions and references for the healthy development of rare disease FSMPs in China.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder posing substantial disease burden in China, with significant impacts on patient quality of life. While conventional immunosuppressants remain fundamental therapy, biologic targeted agents — including B-cell targeting drugs, complement C5 inhibitors, FcRn antagonists, and IL-6R inhibitors — have brought major advances, especially for refractory and MuSK-antibody–positive MG. Increasing availability in China has demonstrated promising clinical outcomes, yet substantial barriers remain. Challenges include high drug costs, limited insurance access, insufficient multicenter clinical evidence, and disparities in physician adoption. China's research is improving, exemplified by local innovation with telitacicept and active participation in global trials, though most biologics remain imported. To maximize benefits, clinical application should be guided by antibody subtype and immunopathology, with individualized, dynamic regimens balancing efficacy, safety, and affordability. High-quality randomized trials, updated guidelines, broader insurance coverage, and R&D investment are urgently needed to promote individualized and accessible MG care in China.

Based on the Policy Modeling Consistency (PMC) index model, this study systematically evaluates 19 national-level and 13 regional-level rare disease policy documents from 2016 to 2025, aiming to reveal the structural characteristics and consistency level of China's rare disease policy system. Using ROSTCM 6.0 software, high-frequency keywords and semantic networks from the policy texts were extracted to identify policy focus and thematic evolution. A PMC evaluation system was constructed to assign values and conduct a visual analysis of the sample policies. Results show that the average PMC index for China's rare disease policies is 5.31 (national level) and 4.94 (local level), falling within the "excellent–acceptable" range overall, indicating that the structure of China's rare disease policy system is well-developed. Among the indicators, policy nature (X2), policy function (X8), and outcome orientation (X4) scored higher, reflecting strategic planning and institutional characteristics at the national level. In contrast, incentive measures (X5), patient support (X6), and social support (X9) scored lower, highlighting deficiencies in research and development incentives, social integration, and long-term support mechanisms. Further comparisons reveal that national policies emphasize top-level design and institutional development. In contrast, local policies focus more on exploratory efforts in medical assistance and policy innovation. To optimize China's rare disease policy system, it is essential to improve incentive and social support systems, promote coordinated legislation between national and local levels, establish a national rare disease information platform and a dedicated fund, and build a comprehensive policy chain.

This study used CiteSpace (version 6.4.R1) to perform a visualization analysis of 3,058 articles on traditional Chinese medicine (TCM) diagnosis and treatment of rare diseases retrieved from the China National Knowledge Infrastructure (CNKI) database, the VIP Chinese Science and Technology Periodical Database (VIP), the Wanfang database (Wanfang), and the Chaoxing database (Chaoxing). The goal was to ascertain the current status of research, hotspots in research, and trends in the development of TCM for rare disease diagnosis and treatment in mainland China, providing insights for future TCM research in this field. Visual maps of annual publication volume, authors, institutions, keywords, and other content have revealed that TCM demonstrates prominent advantages in 5 out of 207 defined rare diseases: idiopathic pulmonary fibrosis, hepatolenticular degeneration (Wilson's disease), osteosarcoma, retinitis pigmentosa, and multiple sclerosis. Potential advantages are identified in treating melanoma, amyotrophic lateral sclerosis, homocysteinemia, primary biliary cholangitis, and lymphangioleiomyomatosis. TCM research on rare diseases focuses on etiology, pathogenesis, and syndrome differentiation-based treatment. Case-control studies and mechanism investigations have been initiated for some conditions, while clinical research is gradually incorporating integrated TCM-Western medicine approaches. However, enhanced team and institutional collaboration, development of multicenter networks, exploration of multidisciplinary research, and clinical studies yielding high-level evidence are still needed to provide quality evidence-based support for clinical decision-making in the TCM treatment of rare diseases.

The high costs of diagnosing and treating rare diseases impose a substantial financial burden on patients and families, underscoring the need to understand reimbursement experiences and unmet needs to improve medical security. Using Dravet syndrome, a severe and lifelong epileptic encephalopathy, as a representative rare disease, this study conducted an online questionnaire survey completed by 161 respondents, including family members or caregivers of patients with Dravet syndrome. The results revealed that most families had insufficient income to cover treatment costs, with patients' annual treatment expenses generally approaching or even exceeding their families' financial capacity, while 41.67% reported that out-of-pocket payments after reimbursement accounted for more than half of their total treatment expense. Surveyed respondents expressed general satisfaction with various medical security models (over 75%), including basic medical insurance, critical illness insurance, medical assistance, commercial health insurance, and charitable aid. However, challenges remain: the limited funding pool and reimbursement capacity of basic medical insurance, the ongoing development of commercial insurance products (e.g., region-specific Huimin insurance), and the lack of guaranteed scale and sustainability of charitable funding. Thus, further improvements in China's medical security for rare disease are imperative. Key priorities include enhancing policy coherence, improving coordination across security models, and increasing the depth of coverage at all levels to alleviate the financial burden on patients.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disorder predominantly driven by anti-aquaporin-4 immunoglobulin G (AQP4-IgG), which mediates astrocyte injury, neuroinflammation, and demyelination. Satralizumab and Inebilizumab represent two promising therapeutic options with distinct mechanisms of action and clinical profiles. This study conducted a retrospective pharmacovigilance analysis of data from the U.S. FDA Adverse Event Reporting System (FAERS) from January 2020 to June 2025 to assess and compare adverse event (AE) reporting signals associated with Satralizumab and Inebilizumab. The analysis revealed a higher number of reported adverse events for Satralizumab compared to Inebilizumab (1,114 cases vs. 349 cases). A higher reporting proportion of AEs was observed in female patients for both drugs, with no statistically significant difference between them (exploratory p = 0.760). The reported AEs for both agents were primarily categorized under System Organ Classes (SOCs) such as infections and infestations and nervous system disorders. Urinary tract infection and pneumonia were among the most frequently reported preferred terms (PTs) for Satralizumab, whereas headache and COVID-19 were prominent for Inebilizumab. Reports classified as serious were more frequent for Satralizumab than for Inebilizumab (exploratory p < 0.01), noting that "seriousness" in FAERS may encompass outcomes related to underlying disease activity. This signal detection study highlights distinct adverse event reporting profiles for these biologics and offers insights that may inform clinical monitoring and personalized treatment strategies in NMOSD. Further studies with rigorous prospective designs are recommended to validate these findings and elucidate the mechanisms underlying the observed adverse events.

Fabry disease (FD) is a rare multisystemic lysosomal storage disorder with diverse pediatric manifestations. This multicenter study analyzed 64 children with FD from the Chinese Children Genetic Kidney Disease Database following establishment of the first national pediatric FD multidisciplinary team (MDT) in April 2020, which expanded to 15 centers by January 2022. Median diagnostic age was 11.4 years in males and 9.4 years in females, with diagnostic delays of 4.4 and 4.0 years, respectively. Family screening accounted for most female diagnoses (72.2%), while 6.5% of males were incidentally detected during genetic testing for other diseases. Missense variants predominated (65.2% males, 66.7% females). Biochemically, males had markedly reduced α-Gal A activity (0.6 ± 0.4 μmol/L/h), and most patients showed elevated globotriaosylsphingosine (Lyso-GL-3), including 87.0% of males and 83.3% of females. Neuropathic pain was the most common initial symptom (52.2% males, 27.8% females; median onset 8 years), primarily acroparesthesia (92.1% and 85.7%, respectively). Other frequent features included anhidrosis/hypohidrosis (58.7% males, 11.1% females). Multisystem involvement included cardiac (arrhythmia n = 11, left ventricular hypertrophy n = 3), pulmonary (obstructive airway disease in 24.2% of males), skeletal (low bone mineral density in 4/7 tested males), and renal manifestations (reduced glomerular filtration rate (GFR) in 3). Thirty-seven patients received enzyme replacement therapy at median ages of 12.9 years (males) and 11.7 years (females). This first nationwide pediatric FD cohort highlights substantial diagnostic delays and underscores the importance of MDT collaboration, family screening, and early recognition to improve outcomes in affected children.

For the vast rare disease patient community in China, science communication is crucial for bridging the information gap. However, the traditional, expert-led knowledge distribution model has proven insufficient to address the dual challenges of resource scarcity and low efficiency in the rare disease field. This paper introduces a new science communication model derived from practice in China. With "Patient-Driven Co-Creation" as its core, this model's ultimate goal transcends traditional information dissemination, aiming to empower the entire ecosystem through systematic value creation. Through an analysis of the practical model of the Wonder Sir platform, this paper proposes for the first time the "Patient Compounding Value Model". This model demonstrates how intangible patient-lived experiences can be systematically transformed into tangible assets capable of driving scientific research, clinical optimization, and public policy, thereby providing a sustainable value-generation mechanism for the resource-scarce rare disease field.