Approval exemplifies commitment to broadening access for patients living with rare diseases globally.

Soliris (eculizumab) has been approved in China for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). Soliris is the first and only complement inhibitor approved for the treatment of NMOSD in China.[1]

The approval by the National Medical Products Administration (NMPA) in China was based on results from the Phase III PREVENT trial.[1] In the trial, Soliris met the primary endpoint of prolonging the time to first adjudicated relapse and reducing the risk of relapse. At 48 weeks, 98 percent of patients treated with Soliris were relapse free compared to 63 percent of patients receiving placebo (relative risk reduction, 94.2%; hazard ratio=0.058; 95% CI: 0.017-0.197; p<0.0001).[1 ]Additionally, 96 percent of patients treated with Soliris remained relapse free at 144 weeks during PREVENT compared to 45 percent of patients treated with placebo.[1]

NMOSD is a rare and debilitating autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves.[2-4] Most people living with NMOSD experience unpredictable relapses, characterised by a new onset of neurologic symptoms or worsening of existing neurologic symptoms, which tend to be severe and recurrent and may result in permanent disability.[5-7] The diagnosed prevalence of adults with NMOSD in China is estimated at approximately 27,000, based on extrapolation of available data.[8]

Xu Yan, MD, PhD, Chief Physician of the Department of Neurology, Peking Union Medical College Hospital and Deputy Leader of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association, said: "The Phase III PREVENT trial established the safety and efficacy of C5 inhibition in reducing the frequency of relapses that can lead to severe and long-term disability for people living with NMOSD. With nearly all patients in the trial achieving relapse-free status at 48 weeks, today's approval marks a fundamental shift in the care of NMOSD in China."

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Patients with NMOSD and their families should not have to live in fear of the next relapse and potential complications. We are proud to bring our first-in-class C5 inhibitor Soliris to the NMOSD community in China, reflecting our commitment to transforming the lives of people living with rare neurological diseases and expanding access to our medicines around the world."

The safety and tolerability profile of Soliris in the PREVENT trial were consistent throughout both the primary treatment period and the open-label extension. The most common adverse events (AEs) were upper respiratory tract infection, headache, nasopharyngitis and nausea.[9]

Soliris is available in China for the treatment of adults and children with paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) (https://www.astrazeneca.com/media-centre/press-releases/2022/astrazeneca-expands-global-footprint-in-rare-disease-with-availability-of-first-alexion-rare-disease-therapy-for-patients-in-china.html) as well as adults with refractory generalised myasthenia gravis (gMG) (https://www.astrazeneca.com/media-centre/press-releases/2023/soliris-approved-in-china-for-the-treatment-of-adults-with-refractory-generalised-myasthenia-gravis.html). Soliris is also approved for multiple indications in many countries around the world.

AstraZeneca established a rare disease business unit in China in September 2021. In the future, the company aims to continue introducing more innovative medicines in China, targeting the complement system and beyond, for the treatment of rare diseases, including PNH, aHUS, gMG, NMOSD, hypophosphatasia, immunoglobulin A nephropathy, lupus nephritis and amyloidosis.

Notes

NMOSD
NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.[2,3] Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4).[10] This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body's defence against infection, to destroy cells in the optic nerve, spinal cord and brain.[2,11,12]

NMOSD most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare.[13,14] People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (e.g., tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement.[4-8,15,16] Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death.[5-7] NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.[17-19]

PREVENT Phase III Trial and Open-Label Extension
PREVENT was a global Phase III, randomised, double-blind, placebo-controlled, multicentre trial evaluating the safety and efficacy of Soliris in adults with anti-AQP4 Ab+ NMOSD. The trial enrolled 143 patients across North America, Argentina, Europe and Asia. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least two relapses in the 12 months prior to the screening visit or three relapses in the previous 24 months, at least one of which occurred in the previous 12 months and an Expanded Disability Status Scale (EDSS) score of 7 or less. Patients were allowed to receive stable maintenance dose of protocol permitted supportive immune suppressive therapies for relapse prevention.[20]

Patients were randomised 2:1 to receive Soliris or placebo and initially received 900 mg of Soliris or placebo weekly for four weeks starting on Day 1 followed by 1200 mg of Soliris or placebo every two weeks starting at Week 4. The primary endpoint was the time to first on-trial relapse as confirmed by an independent adjudication committee. Secondary endpoints included adjudicated annualised relapse rate, quality-of-life measures and EDSS score.[20]

Patients who completed the PREVENT trial or who experienced an adjudicated relapse during the trial were eligible to continue into a long-term extension period and receive Soliris for up to an additional 5.5 years. 95% (119/124) of eligible patients enrolled in the open label extension, of which 78 continued to receive Soliris and 41 were switched from placebo to Soliris.[21]  

Soliris
Soliris (eculizumab) is a first-in-class C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body's immune system. When activated in an uncontrolled manner, the terminal complement cascade over-responds, leading the body to attack its own healthy cells. Soliris is administered intravenously every two weeks, following an introductory dosing period.

Soliris is approved in the US, EU, Japan and China for the treatment of patients with paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome.

Additionally, Soliris is approved in Japan and the EU for the treatment of certain adult and paediatric patients with gMG and in the US and China for certain adults with gMG.

Further, Soliris is approved in the US, EU, Japan and China for the treatment of certain adults with neuromyelitis optica spectrum disorder.

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

Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on social media @AstraZeneca (https://www.linkedin.com/company/astrazeneca?_sm_au_=iVVrT0647WtQQtVS).

Contacts
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References

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