Recommendation based on NEURO-TTRansform Phase III results showing Wainzua demonstrated consistent and sustained benefit improving neuropathy impairment and quality of life versus placebo

基于神经转化III期结果的建议显示，与安慰剂相比，Wainzua表现出一致且持续的益处，可改善神经病变障碍和生活质量

AstraZeneca and Ionis’ Wainzua (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN.1 If approved by the European Commission, Wainzua will be the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector.2-7.

阿斯利康（AstraZeneca）和爱奥尼斯（Ionis）的Wainzua（eplontersen）已被欧盟（EU）人用药品委员会（CHMP）推荐用于治疗成人1期或2期多发性神经病患者的遗传性甲状腺素转运蛋白介导的淀粉样变性，通常称为hATTR PN或ATTRv PN。1如果得到欧盟委员会的批准，Wainzua将是欧盟唯一批准用于治疗ATTRv PN的药物，可以每月通过自动注射器自我管理。

The CHMP based its opinion on the positive NEURO-TTRansform Phase III trial which showed that through 66 weeks, patients treated with Wainzua demonstrated consistent and  sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) versus external placebo.2,8 Wainzua continued to demonstrate a favourable safety and tolerability profile throughout the NEURO-TTRansform trial.2,8.

CHMP基于阳性神经转化III期试验的意见，该试验表明，经过66周的治疗，接受Wainzua治疗的患者在血清甲状腺素转运蛋白（TTR）浓度和神经病变损伤的共同主要终点方面表现出一致和持续的益处，这些终点是通过改良的神经病变损伤评分+7（mNIS+7）和诺福克生活质量问卷糖尿病神经病变（诺福克QoL DN）与外部安慰剂测量的生活质量（QoL）的关键次要终点[2,8]。在整个神经转化试验中，Wainzua继续表现出良好的安全性和耐受性[2,8]。

ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.9,10

ATTRv PN是一种使人衰弱的疾病，在诊断后五年内会导致周围神经损伤并伴有运动障碍，如果不进行治疗，通常会在十年内致命。9,10

Dr Laura Obici, Head of Rare Diseases Unit, Consultant at the Amyloidosis Research and Treatment Centre Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo, Pavia, Italy, said: “This debilitating disease is ultimately fatal if left untreated and can have a significant impact on many aspects of patients’ and caregivers' day-to-day lives.

罕见病部门负责人、淀粉样变性研究与治疗中心Instituto Di Ricovero e Cura a Caratter Scientifico Fondazione Policlinico San Matteo顾问Laura Obici博士说：“如果不及时治疗，这种使人衰弱的疾病最终会致命，并可能对患者和护理人员的日常生活的许多方面产生重大影响。

Having additional amyloidosis treatment options designed to reduce the production of TTR protein at its source would potentially give patients more time and ability to do what matters most to them and offer the hope of living longer with a higher quality of life.'.

拥有额外的淀粉样变性治疗选择，旨在减少TTR蛋白的产生，这可能会给患者更多的时间和能力来做对他们来说最重要的事情，并提供更长时间和更高生活质量的希望。”。

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Due to the progressive nature of polyneuropathy of hereditary transthyretin-mediated amyloidosis, it is critical to have timely diagnosis and new therapies to help people have greater control over this potentially fatal disease.

阿斯利康生物制药业务部门执行副总裁路德·多伯（RuudDobber）表示：“由于遗传性甲状腺素转运蛋白介导的淀粉样变性的多发性神经病具有进行性，因此及时诊断和新疗法至关重要，以帮助人们更好地控制这种潜在的致命疾病。

Today’s recommendation brings Wainzua one step closer for patients in Europe, and if approved, will offer a new treatment option that can provide consistent TTR suppression and results in improved quality of life.”.

今天的建议为欧洲患者带来了更近的一步，如果获得批准，将提供一种新的治疗选择，可以提供一致的TTR抑制并改善生活质量。”。

Wainzua is a once-monthly silencer that provides upstream suppression of TTR production.2,3,11 It is an RNA-targeted medicine designed to reduce production of TTR protein at its source in the liver to potentially treat all types of transthyretin-mediated amyloidosis (ATTR).2,3,11

Wainzua是一种每月一次的沉默剂，可以上游抑制TTR的产生。2,3,11它是一种RNA靶向药物，旨在减少肝脏中TTR蛋白的产生，从而有可能治疗所有类型的运甲状腺素蛋白介导的淀粉样变性（ATTR）。2,3,11

Wainzua was approved under the brand name Wainua for the treatment of ATTRv-PN in the US in December 2023 and is now gaining approvals in additional countries worldwide.11,12 As part of a global development and commercialisation agreement, AstraZeneca and Ionis are commercialising Wainua for the treatment of ATTRv-PN in the US.11,12 The companies are seeking regulatory approval in the EU and other parts of the world, where AstraZeneca has exclusive rest of world commercialisation and development rights. Eplontersen was granted Orphan Drug Designation in the US and in the EU for the treatment of ATTR.11,12.

Wainzua于2023年12月在美国以品牌Wainua获得批准用于治疗ATTRv PN，目前正在全球其他国家获得批准。11,12作为全球发展和商业化协议的一部分，阿斯利康和Ionis正在将Wainua商业化用于治疗美国的ATTRv PN。11,12这些公司正在寻求欧盟和世界其他地区的监管批准，阿斯利康在这些地区拥有全球其他地区的独家商业化和发展权。Eplontersen在美国和欧盟被授予孤儿药称号，用于治疗ATTR.11,12。

Eplontersen is currently being evaluated in the CARDIO-TTRansform Phase III trial for treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), the largest of all ATTR-CM trials to date including over 1,400 participants.11-14

Eplontersen目前正在接受CARDIO-TTRansform III期试验的评估，用于治疗甲状腺素转运蛋白介导的淀粉样心肌病（ATTR-CM），这是迄今为止最大的ATTR-CM试验，包括1400多名参与者。11-14

TTR Amyloidosis

TTR淀粉样变性

ATTR is caused by the accumulation of liver-derived misfolded TTR protein in tissues, such as the heart and the peripheral nerves, causing organ damage and failure.2,15 ATTR then causes complications, leading to cardiovascular, neurological and renal diseases such as heart failure (HF) and chronic kidney disease.15,16 There are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR.15 ATTR is a rapidly progressive and fatal disease that requires timely recognition of symptoms.15,17 ATTR has several phenotypes including ATTR-CM, which predominantly impacts the heart, potentially leading to HF, ATTRv-PN, which predominantly affects the peripheral nervous system, and mixed phenotype, where patients experience symptoms of both.15,18 Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM and about 10,000 – 40,000 patients with ATTRv-PN.11,18.

ATTR是由肝脏衍生的错误折叠的TTR蛋白在心脏和周围神经等组织中的积累引起的，导致器官损伤和衰竭。2,15 ATTR随后引起并发症，导致心血管、神经和肾脏疾病，如心力衰竭（HF）和慢性肾脏病。15,16 ATTR既有遗传性（ATTRv）形式，也有非遗传性（野生型）形式。15 ATTR是一种快速进展的致命疾病，需要及时识别症状。15,17 ATTR有几种表型，包括主要影响心脏的ATTR-CM，可能导致HF，主要影响周围神经系统的ATTRv PN和混合表型，在全世界范围内，患者都有这两种症状[15,18]，估计有300000-500000名ATTR-CM患者和约10000-40000名ATRV PN患者[11,18]。

NEURO-TTRansform

神经转化

NEURO-TTRansform is a global, open-label, randomised trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN.2,19 The trial enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 compared to the external placebo.2,19 The comparison of efficacy and safety for eplontersen versus external placebo was based on data up to week 66.2,19 All patients were then followed on treatment until week 85 and evaluated four weeks after the last dose in an end-of-trial assessment.2,19 Following treatment and the end-of-trial assessments, patients were eligible to enter an open-label extension study, which is still ongoing.2 Full results from the NEURO-TTRansform trial were published in The Journal of the American Medical Association (JAMA) further demonstrating the benefit of Wainzua across the spectrum of ATTRv-PN at 35, 66 and 85 weeks of treatment.2,19.

NEURO-TTRansform是一项全球性的、开放标签的随机试验，用于评估依普隆森在ATTRv PN患者中的疗效和安全性。2,19该试验招募了ATTRv PN 1期或2期的成年患者，与外部安慰剂相比。2,19依普隆森与外部安慰剂的疗效和安全性比较基于截至第66周的数据。2,19所有患者随后接受治疗，直到第85周，并在试验评估结束时在最后一剂后四周进行评估。2,19在治疗和试验评估结束后，患者有资格进入开放标签扩展研究，该研究仍在进行中。2 NEURO-TTRansform试验的全部结果为发表在《美国医学会杂志》（JAMA）上，进一步证明了Wainzua在治疗35,66和85周时在ATTRv PN范围内的益处[2,19]。

Wainzua

温祖阿

Wainzua is a once-monthly silencer that provides upstream suppression of TTR production.2,3,11 It is an RNA-targeted medicine designed to reduce production of TTR protein at its source in the liver to potentially treat all types of ATTR.2,3,11

Wainzua是一种每月一次的沉默剂，可上游抑制TTR的产生。2,3,11它是一种RNA靶向药物，旨在减少肝脏中TTR蛋白的产生，从而有可能治疗所有类型的ATTR。2,3,11

AstraZeneca in CVRM

阿斯利康在CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies.

心血管、肾脏和代谢（CVRM）是生物制药的一部分，是阿斯利康的主要疾病领域之一，也是该公司增长的关键驱动力。阿斯利康通过遵循科学知识，更清楚地了解心脏、肾脏、肝脏和胰腺之间的潜在联系，正在通过减缓或阻止疾病进展，投资一系列器官保护药物，并最终为再生疗法铺平道路。

The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively..

该公司的目标是通过更好地了解CVRM疾病之间的相互关系并针对驱动疾病的机制来改善和挽救数百万人的生命，以便我们能够更早，更有效地检测，诊断和治疗人们。。

AstraZeneca

阿斯利康

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.

阿斯利康（LSE/STO/Nasdaq:AZN）是一家全球科学领先的生物制药公司，专注于肿瘤学，罕见病和生物制药（包括心血管，肾脏和代谢以及呼吸和免疫学）处方药的发现，开发和商业化。

Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. .

阿斯利康的创新药物总部位于英国剑桥，在125多个国家销售，全球数百万患者使用。请访问astrazeneca.com并在社交媒体@astrazeneca上关注该公司。。