Can a Special Fund Bridge the Last Mile? Addressing Out-of-Pocket Challenges in Rare Disease Treatment

The complement system, as a vital component of the human innate immune system, has long been a nightmare for many patients with rare diseases due to its abnormal activation. Paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), neuromyelitis optica spectrum disorder (NMOSD)... These diseases, with their tongue-twisting names, conceal the struggles and hopes of countless patients and their families. Once regarded as "medical islands" due to diagnostic challenges and a lack of effective treatments,

Today, this “isolated island” is being rapidly connected. Precision therapies, represented by complement inhibitors, have been successively launched and introduced into China, included in the national medical insurance coverage, fundamentally rewriting the life trajectories of many patients. Yet this is far from the endpoint; rather, it marks the beginning of a new era. “The rare disease ecosystem requires joint efforts from the government, experts, enterprises, and patient organizations—each party is indispensable,” emphasized Hu Yiqing, Vice President of AstraZeneca China and Head of the Rare Disease Business Unit.

However, the greatest challenge in treating rare diseases currently lies on the payment side. Even with partial coverage by medical insurance, patients still face a significant financial burden, while commercial insurance has its own limitations. In this regard, Hu Yiqing proposed establishing a “Special Fund for Rare Disease Coverage,” which could be funded through diverse sources, including local government subsidies, inclusive commercial health insurance plans (Huiminbao), charitable foundations, and civil affairs assistance.

The complement system consists of various proteins, which typically exist in the blood in an inactive form.

It is understood that when the complement system exhibits defects, dysfunction, or overactivation, it becomes a driving factor for various inflammatory or autoimmune diseases, triggering rare conditions such as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorders (NMOSD).

Since the discovery of complement in the 19th century, research on the complement system and drug development has never ceased. In 2007, pioneered by a leading complement company,AlexionThe first C5 complement inhibitor developed, marking the official launch of complement drugs.

Subsequently, AstraZeneca acquired Alexion for $39 billion. To date, it has investigated the entire complement system cascade, encompassing more than 30 proteins, and characterized all key proteins. Target-specific research has been conducted for each protein, laying the scientific foundation for precision therapy.

Currently, complement inhibitors are widely employed as highly effective clinical therapies across many treatment areas. To ensure that more patients have access to and choices among available medications, Hu Yiqing stated that AstraZeneca has accelerated the introduction of complement inhibitors and other therapies into China. The company has already brought three innovative drugs for rare diseases to Chinese patients, covering five therapeutic areas, with multiple drugs included in the National Reimbursement Drug List (NRDL) for indications such as PNH, aHUS, and gMG.

In fact, AstraZeneca has also been advancing the iteration of complement drugs. “We started with the first generationC5 Complement Inhibitor“...evolving into second- and third-generation, and even fourth- and fifth-generation drugs, including subcutaneous injections and oral formulations, continuously expanding the boundaries of complement therapy,” said Hu Yiqing.

“There are still many candidates in the pipeline. We are currently conducting numerous Phase III clinical trials globally, with China participating synchronously. For instance, we are carrying out a Phase III clinical trial for IgA nephropathy in the nephrology field and conducting clinical trials for transplant-associated thrombotic microangiopathy (TA-TMA) in hematology. These efforts signify that complement therapies will be applied to a broader range of diseases in the future, benefiting more patients with rare diseases,” introduced Hu Yiqing.

Hu Yiqing also revealed that over the next five years, AstraZeneca expects more than 10 new products and new indications to be approved, including C5 inhibitors ranging from first-generation to third-generation and even more advanced agents.

This means that Chinese patients no longer have to endure long waits and can access cutting-edge clinical trial drugs almost simultaneously with the international community. Such synchronicity has greatly accelerated the implementation of innovative therapies in China.

In this process, multinational pharmaceutical companies, including AstraZeneca, have recognized the advantages of China’s vast patient population and the growing research enthusiasm among clinical experts, which has spurred a series of cutting-edge investigator-initiated clinical trials (IIT）。

Hu Yiqing also shared this sentiment: “Many rare disease experts in China have valuable insights and are actively conducting investigator-initiated trials (IITs), which offer us significant inspiration. We hope that more IITs initiated by Chinese experts in the future will help us identify new applications for complement therapies in emerging indications and diseases. This will not only drive innovation in China but also foster global innovation, potentially enabling more rare disease patients worldwide to access innovative complement-targeting therapies.”

With innovative therapies in hand, the ability to deliver them precisely to every patient tests a nation’s healthcare system in terms of organization and execution. For patients with rare diseases—who are often geographically dispersed and face diagnostic challenges—an efficient, standardized, and accessible diagnosis and treatment system is no less critical than the drugs themselves.

Taking rare diseases in the field of hematology as an example, although significant achievements have been made in recent years, there remains a substantial urban-rural disparity. Major medical centers may possess advanced tools for precise diagnosis and maintain high standards of standardized pharmacological treatment, thereby enabling timely care for patients with these rare conditions. However, establishing a comprehensive system for the diagnosis and treatment of rare diseases at the primary care level is challenging. For instance, gene sequencing is not available in all primary care settings. Tests such as flow cytometry for paroxysmal nocturnal hemoglobinuria (PNH) require modern techniques, necessitating both equipment procurement and specialized personnel staffing.

Fortunately, the top-level design at the national level has become clear. The construction of “Centers of Excellence” and the National Rare Disease Diagnosis and Treatment Collaborative Network are becoming core measures to build the framework of the system, providing patients with a systematic framework for tiered diagnosis and treatment and national standardized care.

It is understood that this collaborative network, comprising more than 400 hospitals, constitutes the national-level infrastructure for the diagnosis and treatment of rare diseases. Building on this foundation, companies such as AstraZeneca are supporting the establishment of Centers of Excellence (CoE) for rare diseases. To date, 133 CoEs have been established across China, with plans to support the creation of approximately 800 CoEs covering multiple disease areas by the end of 2025.

Nevertheless, within this network, the sustainability of both R&D and clinical diagnosis and treatment ultimately hinges on a healthy and supportive policy and payment ecosystem. The challenge of rare diseases is not merely a medical issue but also one of social governance. China is exploring multi-stakeholder approaches to tackle this global challenge, aiming to build a new ecosystem characterized by government leadership, shared payment responsibility among multiple parties, and broader societal care.

Meanwhile, research and development in the field of rare disease treatment continues to achieve breakthroughs. Hu Yiqing has repeatedly highlighted the application of gene therapy in rare diseases, stating, “More than 75% of rare diseases are genetically related. Therefore, many of the globally leading gene therapies currently under development primarily target rare diseases. Complement inhibitors also represent a case in point, with their initial indications focused on rare diseases. This demonstrates that the therapeutic technologies employed for rare diseases are among the most advanced across the entire spectrum of medical conditions.”

However, the greatest challenge in treating rare diseases still lies on the payment side. Even though some treatments are covered by medical insurance, they still impose a significant financial burden on patients. For instance, although several complement inhibitors have been included in the National Reimbursement Drug List, patients still face an out-of-pocket expense ratio of 20%–40%. Given that annual treatment costs for these drugs range from RMB 200,000–300,000 to over RMB 1 million, the financial burden on patients remains substantial.

To better alleviate the financial burden on patients, commercial insurance is also actively exploring payment solutions. However, as commercial insurers are profit-driven, pre-existing conditions are generally excluded from coverage, and many patients with rare diseases already have a prior diagnosis.

Payment Innovation and Multi-tiered Coverage: The Core Focus in Addressing the Affordability ChallengeThe current consensus is that reliance solely on the basic national health insurance scheme is insufficient; a multi-tiered coverage system must be established.

“After national medical insurance has covered a portion of the costs, we hope that provincial-level authorities will introduce supplementary funds and multi-tiered coverage mechanisms to further reduce patients’ out-of-pocket expenses. Given that the return on investment for innovative therapies makes it unfeasible to lower prices to the range required by national medical insurance, establishing a national special fund dedicated to rare diseases and encouraging the use of innovative drugs would allow high-cost medications to be included in such coverage. This would enable patients with rare diseases to access the best available treatments and return to normal lives.”

Hu Yiqing has repeatedly called for the establishment of a “Special Protection Fund for Rare Diseases,” which could be funded through diverse sources, including local government subsidies, inclusive commercial health insurance (Hui Min Bao), charitable foundations, and civil affairs assistance.

In fact, effective prevention and control of rare diseases yield multiple social benefits. This not only benefits patient populations but also constitutes a critical livelihood project. First, it strengthens the national health safety net, preventing families from falling back into poverty due to illness. Second, as more than half of rare diseases manifest in childhood, state-provided coverage can significantly bolster public confidence. Third, supporting reimbursement for innovative orphan drugs helps drive pharmaceutical technological innovation. Rare diseases serve as an important testing ground for new drug development; as international experience has shown, leading Chinese pharmaceutical companies can achieve technology transfer and revenue generation by developing innovative drugs and exporting them overseas. In light of this, Hu Yiqing argues that efforts should not be confined within the basic medical insurance framework; instead, a special-case approach should be adopted to advance rare disease coverage.

The conclusion of the 2nd Complement Day marks not only a summary of one phase but also the beginning of a new chapter. China’s exploration in the field of complement and related rare diseases has demonstrated a systematic approach to problem-solving: it is no longer merely about single-point drug introductions or fragmented charitable aid, but rather a profound and comprehensive transformation underpinned by three pillars—“scientific innovation, diagnosis and treatment systems, and policy ecosystems.”

This path has demonstrated that only by seamlessly integrating researchers’ cutting-edge breakthroughs, hospitals’ efficient organization, forward-looking policy support, and societal attention can we build a hopeful, dignified, and predictable future for those “minority” patients who were once forgotten. China’s practice, which draws on global experience while maintaining distinct characteristics, is drawing the world’s attention with its proposed “Chinese Solution.”

Although the road ahead remains long—“we still lack effective pharmacological treatments for 95% of patients,” payment challenges urgently need to be resolved, and regional disparities must be bridged—the direction is clear, the system is taking shape, and the ecosystem is becoming increasingly vibrant. Starting from complement therapy, this grand experiment in China’s rare disease endeavor holds significance far beyond the diseases themselves; it serves as a stress test for the modernization and humanization of a nation’s healthcare system, and represents a profound practice of the common prosperity principle that “no one should be left behind.” The future is promising, yet the mission remains arduous and the journey long.