AstraZeneca Announces NMPA Approval of Soliris® (Eculizumab) for Adults with AQP4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder in China

 This approval further deepens AstraZeneca's commitment to patients with rare diseases worldwide.

ShanghaiOctober 18, 2023PR Newswire -- The China National Medical Products Administration has approved eculizumab injection (brand name: Soliris).^®，Soliris^®) for the treatment of adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Eculizumab is the first and only complement inhibitor approved in China for the treatment of NMOSD.^[1]。

This approval of eculizumab by the National Medical Products Administration (NMPA) of China is primarily based on the results of the pivotal Phase III PREVENT study.^[1]. The study results showed that, based on the time to recurrence during the first adjudication period, eculizumab treatment significantly reduced the risk of recurrence with statistical and clinical significance. At week 48, 98% of patients treated with eculizumab (63% of placebo-treated patients) were recurrence-free (relative risk reduction of 94.2%; hazard ratio=0.058; 95% CI: 0.017-0.197; p<0.0001), and the treatment benefit persisted until week 144.^[1]Moreover, within the 144-week PREVENT study, 96% of patients treated with eculizumab remained relapse-free, compared to only 45% in the placebo group.^[1]。

NMOSD is a rare and debilitating autoimmune disease of the central nervous system that primarily affects the optic nerves and spinal cord.^[2]-[4]Most patients with NMOSD experience multiple relapses, which may present with new neurological symptoms or worsening of existing neurological symptoms, leading to permanent disability due to repeated relapses.^[5]-[7]Based on the available data, it is estimated that approximately 27,000 adults in China are currently diagnosed with NMOSD.^[8]。

Professor Yan Xu, Chief Physician of the Department of Neurology at Peking Union Medical College Hospital, and Deputy Head of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association"Noted: "The frequent relapses of NMOSD often lead to long-term severe disability in patients. Therefore, we are very pleased to see that the Phase III PREVENT study has confirmed the safety and efficacy of the C5 complement inhibitor in reducing NMOSD relapses, with almost all patients treated with eculizumab showing no relapse at 48 weeks. The approval of eculizumab for the treatment of adult NMOSD in China marks a significant advancement in the field of treatment in our country."

CEO of Raison PharmaceuticalsMarc Dunoyer"Patients with NMOSD and their families should not live in fear of relapses and potential complications. Eculizumab is the world's first C5 complement inhibitor for the treatment of NMOSD, and we are delighted to introduce it in China, providing more innovative treatment options for NMOSD patients. The approval of eculizumab further enhances its accessibility in the global market and fully demonstrates our commitment to improving the quality of life for patients with rare neurological disorders."

Leon Wang, Executive Vice President of AstraZeneca PLC and President of International Business & China"Providing patients with high-quality medical services is our unwavering初心. We look forward to eculizumab bringing long-term survival benefits to NMOSD patients. In the future, we will continue to comprehensively and rapidly introduce innovative global medicines, and work with like-minded partners to build a robust rare disease diagnosis and treatment ecosystem, striving to create a better future for the NMOSD community and the broader rare disease population."

The safety and tolerability of eculizumab were consistent during the PREVENT study and its open-label extension study. The most common adverse reactions during treatment were upper respiratory tract infections, headaches, nasopharyngitis, and nausea.^[9]。

Currently, eculizumab has been approved in China for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults and children, atypical hemolytic uremic syndrome (aHUS), and refractory generalized myasthenia gravis (gMG) positive for anti-acetylcholine receptor (AChR) antibodies in adults. It has also been approved for multiple indications in many countries worldwide.

In September 2021, AstraZeneca established a Rare Disease Business Unit in China and has continued to introduce innovative rare disease drugs. Globally, AstraZeneca is advancing innovation across multiple rare disease areas involving both complement and non-complement systems, including Paroxysmal Nocturnal Hemoglobinuria, Atypical Hemolytic Uremic Syndrome, Generalized Myasthenia Gravis, Neuromyelitis Optica Spectrum Disorders, Hypophosphatasia, IgA Nephropathy, Lupus Nephritis, and Amyloidosis, among other rare disease fields.

*Statement: As of the date of publication, eculizumab is the only drug approved for treatment in China.NMOSDComplement inhibitor. This article involves products or indications not approved in China, and AstraZeneca does not recommend the use of any unapproved drugs.

About Neuromyelitis Optica Spectrum Disorders

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare central nervous system disease in which the immune system is abnormally activated, attacking healthy tissues and cells in the central nervous system.^[2],[3]About three-quarters of patients with neuromyelitis optica spectrum disorders (NMOSD) will produce antibodies that bind to a specific protein, AQP4, presenting as anti-AQP4 antibody positive.^[10]The complement system is part of the immune system and is crucial for the body's defense against infections, but this specific binding leads to abnormal activation of the complement system, resulting in damage to cells in the optic nerve, spinal cord, and brain.^{[2],[11],[12]}。

Neuromyelitis Optica Spectrum Disorders are common in women and generally begin to develop in the 30s. Men and children may also be affected, but such cases are rarer in the population.^[13],[14]NMOSD patients may experience vision problems, severe pain, loss of bladder or bowel function, abnormal skin sensations (such as tingling or sensitivity to heat and cold), and impacts on coordination or motor abilities.^{[4]-[8],[15],[16]}Most patients with NMOSD experience multiple relapses. Each relapse can lead to increased disability, including vision loss, paralysis, and even premature death.^[5]-[7]NMOSD is distinct from other central nervous system diseases such as multiple sclerosis. Its diagnosis is not only prolonged but also prone to misdiagnosis.^[17]-[19]。

Regarding Phase IIIPREVENTAnd Open-Label Extension Study

PREVENT is a global Phase III randomized, double-blind, placebo-controlled multicenter study designed to evaluate the safety and efficacy of eculizumab in adult patients with AQP4 antibody-positive NMOSD. The study enrolled 143 AQP4 antibody-positive NMOSD patients in North America, Argentina, Europe, and Asia. Patients included in the study had at least two relapses within the past 12 months or three relapses within the past 24 months, with at least one occurring within the past 12 months, and an Expanded Disability Status Scale (EDSS) score of 7 or lower. To prevent relapses, patients could receive supportive immunosuppressive therapy at a stable dose within the permitted range.^[20]。

Patients were randomized 2:1 to receive either eculizumab or placebo. Eculizumab or placebo was administered at a dose of 900 mg weekly for the first four weeks, followed by a maintenance dose of 1200 mg every two weeks. The primary endpoint was the time to first clinical relapse confirmed by an independent review committee. Secondary endpoints included adjudicated annualized relapse rate, quality of life measures, and EDSS score.^[20]。

Patients who completed the PREVENT study or experienced an adjudicated relapse during the study were eligible to continue into the long-term extension study, receiving eculizumab for up to 5.5 years. Ninety-five percent (119/124) of patients participated in the open-label extension treatment, with 78 continuing on eculizumab and 41 switching from randomized placebo treatment to eculizumab.^[21]。

About Eculizumab

Eculizumab is the world's first C5 complement inhibitor, which functions 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. Eculizumab is administered intravenously once every two weeks after the induction dosing period.

Eculizumab has been approved in the United States, the European Union, Japan, and China for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

In addition, eculizumab has been approved in Japan and the EU for the treatment of specific adult and pediatric patients with generalized myasthenia gravis (gMG), and in the US and China for the treatment of specific adult patients with generalized myasthenia gravis (gMG).

Eculizumab is also approved in the United States, the European Union, Japan, and China for the treatment of specific adult patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).

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

About Raison Pharmaceuticals

Alexion, AstraZeneca Rare Disease is a subsidiary of AstraZeneca's rare disease business. In 2021, AstraZeneca acquired Alexion to enter the rare disease field. With over 30 years of dedication to the rare disease area, Alexion is committed to providing life-changing medicines for patients with rare diseases and their families. Alexion’s research and development focuses on novel molecules and targets within the complement system, concentrating on six major disease areas: hematology, nephrology, central nervous system, metabolism, cardiovascular, and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices worldwide, benefiting patients in more than 50 countries.

About AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a science-led global biopharmaceutical business focused on the discovery, development, and commercialization of prescription medicines, primarily in Oncology, as well as Biopharmaceuticals including Cardiovascular, Renal & Metabolism, Respiratory & Immunology, Vaccines & Infection, and Rare Diseases. Headquartered in Cambridge, UK, AstraZeneca operates in over 100 countries worldwide, delivering innovative medicines to millions of patients globally. For more information, please visitwww.astrazeneca.comAnd you can follow on social media@AstraZeneca。

About AstraZeneca China

Since entering China in 1993, AstraZeneca has focused on therapeutic areas with the most urgent needs for Chinese patients, including oncology, cardiovascular, renal, metabolism, respiratory, digestive, rare diseases, vaccines and antibodies, as well as autoimmune diseases, bringing nearly 40 innovative drugs to China. AstraZeneca's China headquarters and Global R&D Center China are located in Shanghai, with global production and supply bases established in Wuxi, Taizhou, and Qingdao, delivering high-quality medicines to nearly 70 global markets. In recent years, the company has set up regional headquarters in Beijing, Guangzhou, Hangzhou, Chengdu, and Qingdao. AstraZeneca also collaborates with partners to build a diversified international innovation-driven healthcare ecosystem through its "three-innovation drivers," including the China Commercial Innovation Center (CCiC), International Life Science Innovation Park (iCampus), and AstraZeneca Zhongjin Healthcare Industry Fund, jointly promoting the long-term development of regional economies and the broader healthcare industry. Today, China has become AstraZeneca’s second-largest market globally.

References

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^[20].  ClinicalTrials.gov. A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial to Evaluate the Safety and Efficacy of Eculizumab in Patients With Relapsing Neuromyelitis Optica (NMO). NCT Identifier: NCT01892345. Available here. Accessed July 2023.

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