AstraZeneca's Rare Disease Drug Soliris® (Eculizumab) with Three Indications Included in China's National Reimbursement Drug List

Help Improve Drug Accessibility for Rare Disease Patients

ShanghaiDecember 13, 2023PR Newswire -- Today, the National Healthcare Security Administration and the Ministry of Human Resources and Social Security announced the "National Basic Medical Insurance, Work-related Injury Insurance, and Maternity Insurance Drug Catalog (2023)" (hereinafter referred to as the "Medical Insurance Catalog"), which will be officially implemented on January 1, 2024. As the world's first C5 complement inhibitor, Suliri^®(General name: Eculizumab Injection) has had three of its approved indications in China included in the National Reimbursement Drug List (NRDL). These include the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in adults and children, as well as refractory generalized myasthenia gravis (gMG) positive for anti-acetylcholine receptor (AChR) antibodies in adults. This will effectively improve patient access to this innovative drug for the three rare diseases, thereby achieving health benefits and improving quality of life, while significantly reducing the financial burden of treatment on patients' families.

Zhang Shuyang, President of Peking Union Medical College HospitalSaid: "When will rare disease patients be able to access innovative drugs and freely do what they want? This has always been the appeal of patients and also our goal as doctors. In recent years, with the implementation of the annual negotiation for the National Medical Insurance Catalog and related policies, the medical security level for rare disease patients has significantly improved, bringing them closer to being able to afford these drugs. However, we still see obstacles in the ‘last mile’ when it comes to patients accessing these drugs. For example, potential issues such as whether these drugs will face hospital entry barriers or drug ratio restrictions, whether inpatient drug use will be limited by DRG/DIP payments, and whether outpatient drug coverage is sufficient. These factors may prevent some rare disease patients in certain regions from fully enjoying the medical and insurance benefits they deserve. Therefore, rare diseases are not just a medical issue but also a social one. In the future, we need to continue promoting the rapid inclusion of rare disease medications into special outpatient and chronic disease categories to ensure they receive medical insurance benefits. Through the joint efforts of multiple parties, we must work to address the ‘last mile’ of medical insurance medication accessibility, bringing happiness to thousands of families affected by rare diseases."

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hemolytic disease caused by somatic mutations in the PIG-A gene at the hematopoietic stem cell level, with a five-year mortality rate as high as 35%.^[1]. Moreover, the disease is more common in young adults, with patients aged 20-40 accounting for approximately 77%.^[2], 23% of PNH patients are hospitalized due to PNH complications^[3], nearly 70% of blood transfusion needs^[4]，seriously affecting the daily life and work of patients and caregivers.Professor Fu Rong, Vice President of Tianjin Medical University General Hospital and Director of the Hematology Center"This age group of patients are often the backbone of the family, and the impact of the disease on the patient's health and the burden of treatment bring immense pressure to their families. Before the advent of complement inhibitors, the main treatment for PNH was symptomatic, including blood transfusions, glucocorticoids, and immunosuppressants. However, traditional therapies face many challenges in controlling hemolysis and preventing renal function damage. The improvement in the accessibility and affordability of complement inhibitors will help address these issues."

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare and fatal condition caused by the overactivation of the body's complement system attacking endothelial cells, leading to complement-mediated thrombotic microangiopathy (CM-TMA). The disease has an abrupt onset, with a higher incidence in children than in adults, and approximately 25% of pediatric patients die during the acute phase.^[5]Nearly 50% of aHUS patients can progress to end-stage renal disease (ESRD), with a mortality rate of 25%.^[6]Clinically, about half of aHUS patients respond to plasma exchange, but long-term plasma exchange may lead to hypotension, catheter-related infections, and complications. Comprehensive treatment includes red blood cell infusion, dialysis, and kidney transplantation, but the effects vary from person to person.^[7]As a complement inhibitor, eculizumab offers a new treatment option for patients with rare diseases.

Generalized Myasthenia Gravis (gMG) is a rare, chronic autoimmune disease caused by impaired neuromuscular junction transmission. Initial symptoms may include slurred speech, double vision, drooping eyelids, and generalized weakness; as the disease progresses, more severe symptoms such as swallowing difficulties, extreme fatigue, and respiratory failure may occur.^[8],[9], of which about 10-15% are refractory patients, posing a relatively challenging problem in clinical practice.Professor Chongbo Zhao, Department of Neurology, Huashan Hospital, Fudan UniversityRefractory patients are characterized by younger age of onset, a higher proportion of females, more severe clinical symptoms, and poorer quality of life. According to relevant statistics, 17% of patients will develop respiratory failure within one year.^[10]; The average length of hospital stay was 22.19 days per year.^[10]In clinical practice, these refractory patients who respond poorly or are intolerant to conventional treatments, if not properly controlled, can experience a significant impact on daily life and may even progress to life-threatening crises. Such patients have many unmet needs in treatment and an urgent expectation for safer and more effective innovative drugs.

Li Lin Kang, Executive Chairman of the China Rare Disease Alliance and Vice President of the Chinese Hospital AssociationSaid: "On the road to achieving universal health, not a single rare disease patient can be left behind. In recent years, the Party and the state have paid high attention to the improvement of diagnosis and treatment levels for rare diseases and are committed to enhancing the drug security for rare diseases. The inclusion of multiple rare disease drugs in the 'Medical Insurance Catalog' is good news. We look forward to continuous improvement in the medical security for rare diseases through collaborative innovation from society, enterprises, and the healthcare system, thereby enhancing patients' access to and affordability of medications."

PNHFounder of Patient Family, Jiajia"The inclusion of Eculizumab in the National Medical Insurance Catalogue is highly significant for every patient. It fills a long-awaited gap in patient accessibility. Over the years, we have witnessed the continuous efforts of the country and the government to ensure medication for rare disease patients, bringing us closer to accessing ‘innovative drugs.’ However, we still see challenges in the ‘last mile’ of actual drug usage by patients. For example, some rare disease patients in certain regions still face difficulties such as ‘difficulty in getting drugs into hospitals,’ ‘difficulty in accessing medication,’ and ‘difficulty in reimbursement.’ I also hope that after this version of the medical insurance catalog is officially implemented, the rare disease medical insurance channels across China will be smooth, allowing patients in need to truly afford and access their necessary medications."

Leo Wang, Executive Vice President of AstraZeneca Global, President of International Business and China"‘Patient-centered,' AstraZeneca spares no effort to meet patients' needs by actively engaging in and continuously exploring the challenging field of rare diseases, with the aim of enabling patients to access high-quality medical services. Not only do we ensure the comprehensive and rapid introduction of innovative medicines globally, but we also collaborate with multiple parties, including the government, to ensure patients can afford their medications, as this is the only way to realize the true value of these innovative drugs. In the future, AstraZeneca will continue to support all partners in exploring multi-level security models to help alleviate the medical burden on patients with rare diseases and enhance their healthcare benefits. Additionally, we will actively participate in building a sound rare disease diagnosis and treatment ecosystem, creating a standardized network of diagnosis, treatment, and protection for more rare disease communities, working together towards a future where rare diseases are no longer rarely treated."

Regarding Paroxysmal Nocturnal Hemoglobinuria (PNH）：PNH is a chronic, progressive, life-threatening rare blood system disease characterized by complement-mediated hemolysis (red blood cell destruction). PNH can occur at any age but is more common in young and middle-aged adults. The most devastating consequence of PNH hemolysis is the formation of blood clots, which can damage organs and lead to death.

About Atypical Hemolytic Uremic Syndrome (aHUS）：aHUS is a persistent complement-mediated systemic thrombotic microangiopathy, often presenting acutely and severely. Uncontrolled, ongoing excessive complement activation leads to complement-mediated thrombotic microangiopathy (CM-TMA), which may result in the formation of blood clots in small blood vessels throughout the body. Patients with aHUS may face the risk of multiple TMA recurrences, causing sudden, life-threatening, irreversible damage to the kidneys and other vital organs.

About Generalized Myasthenia Gravis (gMG）: Generalized myasthenia gravis (gMG) is a rare autoimmune disease, mainly characterized by loss of muscle function, fluctuating weakness of skeletal muscles, and severe debilitation.^[11]。

Acetylcholine receptor (AChR) antibodies are the most common pathogenic antibodies in MG, with approximately 80% of patients testing positive for AChR antibodies, which means that AChR antibodies bind to the signal receptors at the neuromuscular junction (NMJ).^{[11],[12],[13],[14],[15]}. This combination activates the complement system, which plays a crucial role in both innate immunity and antibody-mediated immunity. Activation of the complement leads to the formation of the membrane attack complex (MAC), resulting in neuromuscular junction transmission impairment. This subsequently causes abnormal neuromuscular transmission and the characteristic muscle weakness associated with MG.^[11]。

gMG can occur at any age, with more females than males before the age of 40 and more males than females after the age of 60.^[16],^[17],[18]The initial symptoms may include slurred speech, double vision, drooping eyelids, and lack of balance; as the disease progresses, more severe symptoms such as swallowing difficulties, choking, extreme fatigue, and respiratory failure may occur.^[19],[20]

About Eculizumab:Eculizumab is the world's first C5 complement inhibitor, which works by selectively inhibiting the activation of terminal complement C5. The complement system is an important part of the human immune system, but when the complement is activated in an uncontrolled manner, it may lead to the body attacking its own healthy cells. After the induction dosing period, eculizumab is administered intravenously once every two weeks.

Eculizumab has been approved in markets such as the United States, the European Union, Japan, and China for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and certain adults with generalized myasthenia gravis (gMG). Additionally, eculizumab has also been approved in the United States, the European Union, Japan, and China for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

Eculizumab is not indicated for the treatment of Shiga-toxin E. coli-related haemolytic uraemic syndrome.

About AstraZeneca:AstraZeneca (LSE/STO/Nasdaq: AZN) is a science-led global biopharmaceutical company focused on the research, development, manufacturing, and marketing of prescription medicines, primarily concentrating on oncology, rare diseases, and biopharmaceutical areas including cardiovascular, renal, metabolic, respiratory, and immunology. AstraZeneca’s global headquarters is located in Cambridge, UK, with operations in over 100 countries worldwide, providing innovative medicines to millions of patients globally. For more information, please visitwww.astrazeneca.com。

About AstraZeneca China:Since entering China in 1993, AstraZeneca has focused on the treatment areas with the most urgent needs for Chinese patients, including oncology, cardiovascular, renal, metabolism, respiratory, digestive, rare diseases, vaccines and antibodies, as well as autoimmunity. It has brought nearly 40 innovative drugs to China. AstraZeneca’s China headquarters and its Global R&D Center China are located in Shanghai, with global production and supply bases established in Wuxi, Taizhou, and Qingdao. These facilities have delivered high-quality medicines to nearly 80 global markets. In recent years, the company has set up regional headquarters in Beijing, Guangzhou, Hangzhou, Chengdu, and Qingdao. AstraZeneca has also partnered with collaborators to create an innovative "troika," including the China Commercial Innovation Center (CCiC), the International Life Science Innovation Park (iCampus), and the AstraZeneca Zhongjin Healthcare Industry Fund, building a diversified international innovation-driven healthcare ecosystem to jointly promote the long-term development of regional economies and the broader healthcare industry. Today, China has grown to become AstraZeneca's second-largest market globally.

[1] N Engl J med 1995；333:1253-1258.

[2] Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 Edition): 552

[3] Cherry A M , Arber D , Moore E .Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry Haematologica haematol.[J]. 2014.

[4] Lee JW，et al. Blood (2014) 124 (21): 5151.

[5] Liu Xiaorong, Shen Ying, Fan Jianfeng, et al. Expert Consensus on the Diagnosis and Treatment of Atypical Hemolytic Uremic Syndrome in Chinese Children[J].

[6] Afshar-Kharghan V.Hematology Am Soc Hematol Educ Program. 2016; 2016(1):217-225

[7] Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 Edition): 547-551

[8] Myasthenia Gravis Fact Sheet. National Institutes of Neurological Disorders and Stroke. 2020. Available here. Accessed March 2022.

[9] Ding J, Zhao S, Ren K, et al. Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology. 2020;20(238).

[10] Clinical and Experimental Neuroimmunology 10 (2019) 61–68.

[11] Howard JF. Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences. 2017;1412(1), 113-128.

[12] Anil R, Kumar A, Alaparthi S, et al. Exploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry - The EXPLORE-MG registry. J Neurol Sci. 2020;414:116830.

[13] Oh SJ. Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. Journal of Clinical Neurology. 2009;5(2):53-64.

[14] Tomschik M, Hilger E, Rath J, et al. Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis. Neurology. 2020;95(10):e1426-e1436.

[15] Hendricks TM, Bhatti MT, Hodge D, et al. Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019;205:99-105.

[16] Howard JF. Clinical Overview of MG. 2015. Available here. Accessed March 2022.

[17] Myasthenia Gravis. National Organization for Rare Disorders (NORD). Available here. Accessed March 2022.

[18] Sanders DB, Raja SM, Guptill JT, et al. The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve. 2020;63(2), 209-216.

[19] Myasthenia Gravis Fact Sheet. National Institutes of Neurological Disorders and Stroke. 2020. Available here. Accessed March 2022.

[20] Ding J, Zhao S, Ren K, et al. Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology. 2020;20(238).