Beyfortus approved in Japan for the prevention of RSV disease in infants

First and only RSV preventive option for broad infant population authorised for use in Japan

AstraZeneca and Sanofi’s Beyfortus (nirsevimab), a long-acting monoclonal antibody, 在日本被批准用于预防由呼吸道合胞病毒(RSV)引起的所有新生儿下呼吸道疾病(LRTD), infants and children entering their first RSV season, and the prevention of RSV LRTD in neonates, infants and children at risk of serious RSV infection entering their first or second RSV season.¹ Beyfortus is anticipated to be available for the upcoming 2024/25 RSV season, in line with existing Japanese guidelines.

Beyfortus is the first preventive option developed to protect a broad infant population against RSV LRTD, including protecting those infants born healthy at term, or preterm, or with specific health conditions that make them vulnerable to severe disease. The approval by the Japanese Ministry of Health, Labour and Welfare is based on three Beyfortus pivotal late-stage clinical trials. Across all clinical endpoints, a single dose of Beyfortus demonstrated consistent efficacy against RSV LRTD extending through five months, the duration of a typical RSV season.^2-5

More than 100,000 cases of RSV LRTD in infants are reported every year in Japan including healthy infants born at term.⁶

Dr. Hiroyuki Moriuchi, Professor and Head of Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, said: “This is an important milestone in the fight against RSV in infants. Almost all children are affected by RSV by the age of two and all infants, including those born healthy and at term, can be at risk. RSV causes a significant burden for children, 他们的家庭和医疗系统可能导致婴儿严重感染的长期后果. Beyfortus 是否能在整个RSV季节保护婴儿，其批准对日本RSV疾病的预防和控制做出了重要贡献.”

Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “The approval of Beyfortus 这意味着首次有可能预防日本所有婴儿因呼吸道合胞病毒引起的严重呼吸道疾病，并减轻卫生保健系统的传染病负担. Beyfortus 这反映了澳门葡京网赌游戏对科学开发预防方案的承诺，以支持最脆弱的患者群体，澳门葡京赌博游戏期待着做出 Beyfortus available in Japan for the 2024/25 season.” 

Beyfortus has received approval in the European Union, US and China.

Notes

Japan Beyfortus indication¹
The following groups of neonates, infants or children at risk of serious RSV infection entering their first or second RSV season, should meet at least one of the following criteria:

• In the early stage of first RSV season

o  Infants born at 28 weeks’ gestation or earlier and less than 12 months of age

o  Infants born at 29 to 35 weeks' gestation and less than 6 months of age

• In the early stage of first and second RSV season

o  Neonates, 在过去6个月内接受过一种慢性肺病治疗的婴儿或小于24个月的儿童

o  Neonates, infants or children less than 24 months of age with hemodynamically significant congenital heart disease

o   Neonates, infants or children less than 24 months of age with immunocompromised conditions

o   Neonates, infants or children less than 24 months of age with Down syndrome

Global pivotal clinical trials
The Phase IIb (Trial 03) study was a randomised, placebo-controlled trial designed to measure the efficacy of Beyfortus against medically attended (MA) Lower Respiratory Tract Infection (LRTI) through 150 days post-dose. 29至小于35周胎龄的健康早产儿随机(2:1)接受单次50mg的肌内注射 Beyfortus or placebo regardless of weight.^1,4

The Beyfortus 给药方案是基于对IIb期数据的进一步探索确定的，并在随后的试验中作为50mg单剂量用于体重小于5kg的患者, or a single 100mg dose for those who weigh 5kg or greater.^1,4

The MELODY Phase III study (Trial 04) was a randomised, double-blind, placebo-controlled trial conducted across 21 countries designed to determine efficacy of Beyfortus against medically attended LRTI through 150 days after dosing, versus placebo, 健康足月和晚期早产儿(胎龄35周或更大)进入第一个RSV季节.^1-3

The MEDLEY (Trial 05) was a Phase II/III, randomised, double-blind, Synagis (palivizumab)-controlled trial with the primary objective of assessing safety and tolerability for Beyfortus 在小于35周胎龄的早产儿和患有先天性心脏病(CHD)和/或早产儿慢性肺部疾病(CLD)的婴儿中接受治疗 Synagis. Between July 2019 and May 2021, 在每个接受治疗的早产儿和CLD/CHD队列中，共有925名进入第一个RSV季节的婴儿被随机分配(2:1) Beyfortus or Synagis. 来自CLD/CHD队列的262名24个月以下的儿童在第二个RSV季节继续进行试验. Safety was assessed by monitoring the occurrence of adverse events through 360 days post-dose.

The results of MELODY, MEDLEY Phase II/III and the Phase IIb trials demonstrate that a single dose of Beyfortus helps protect infants during their first RSV season against RSV disease. This broad infant population includes healthy term, late preterm and preterm infants, as well as infants with specific health conditions that make them vulnerable to severe RSV disease.^1,5

These trials formed the basis of regulatory submissions which began in 2022.

Results

Phase IIb trial (Trial 03)
The primary endpoint of the Phase IIb study was met, reducing the incidence of medically attended LRTI caused by RSV by 70.1% (95% CI: 52.3, 81.2) compared to placebo. The event rates were 2.6% in treatment arm vs 9.5% in placebo arm. Between November 2016 and December 2017, 1,453 infants were randomised (Beyfortus, n=969; placebo, n=484) at the RSV season start. Research was conducted by AstraZeneca in both hemispheres, at 164 sites in 23 countries. Data were published in NEJM in July 2020.^1,4

In a prespecified secondary endpoint, Beyfortus reduced medically attended RSV LRTI with hospitalisation by 78.4% (95% CI 51.9, 90.3) versus placebo. Observed events were 0.8% in treatment arm vs 4.1% in placebo arm.¹ A subgroup analysis by body weight indicated a lower efficacy in infants >5 kg vs <5kg. IIb期研究的事后分析结果显示，在体重小于5kg的婴儿亚组中使用推荐的50mg剂量的效果 Beyfortus against medically attended RSV LRTI and medically attended RSV LRTI with hospitalisation was 86.2% (95% CI 68.0, 94.0) and 86.5% (95% CI 53.5, 96.1) respectively.^1,7

MELODY Phase III trial (Trial 04)
The primary endpoint of the MELODY Phase III trial was met, reducing the incidence of medically attended LRTI, such as bronchiolitis or pneumonia, caused by RSV by 74.5% (95% confidence interval (CI) 49.6, 87.1; P<0.001) compared to placebo.³ The event rates were 1.2% in treatment arm vs 5% in placebo arm. The Beyfortus dosing regimen was determined based on further exploration of the Phase IIb data and was 50mg<5kg and 100 mg >=5kg. The efficacy of Beyfortus against the secondary endpoint of hospitalisation was 62.1% (95% CI: -8.6, 86.8). Observed events were 0.6% in treatment arm vs 1.6% in placebo arm. Between July 2019 and March 2020, 1,490 infants were randomised to receive either Beyfortus or placebo at the RSV season start. Initial data from the MELODY Primary Cohort were published in NEJM in March 2022.^1,5

MEDLEY Phase II/III trial (Trial 05)
Serum levels of Beyfortus 在本试验中给药后(第151天)与MELODY III期试验中观察到的结果相当, 这表明在这一人群中，与健康足月婴儿和晚期早产儿的保护作用相似. In the first RSV season, the incidence of medically attended RSV LRTI through 150 days post dose was 0.6% (4/616) in the Beyfortus group and 1.0% (3/309) in the Synagis group. In the second RSV season, there were no cases of medically attended RSV LRTI through Day 150 in children who received either Beyfortus or Synagis. Data were published in the New England Journal of Medicine (NEJM) in March 2022.^1,5

The safety profile of Beyfortus was similar to Synagis 在MEDLEY II/III期试验中，与MELODY和IIb期试验中研究的健康足月和早产儿的安全性一致. While uncommon, the most reported adverse reactions were: rash 14 days post-dose (the majority of which were mild to moderate); non-serious injection site reactions within 7 days post-dose.^1,3,5

Beyfortus
Beyfortus (nirsevimab) is a single dose long-acting antibody, developed and commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca’s YTE technology. 它旨在保护在第一个RSV季节出生或进入第一个RSV季节的婴儿，以及24个月以下的儿童，他们在第二个RSV季节仍然容易患上严重的RSV疾病.  Beyfortus, provided directly to newborns and infants as a single dose, offers rapid protection via an antibody to help prevent LRTD caused by RSV, without requiring activation of the immune system.

Beyfortus 可在呼吸道合胞病毒流行季节开始时给药，或在该季节出生的婴儿接种时给药.¹

Beyfortus 是否已被世界各地的几个主要监管机构授予监管指定，以促进加速发展. 其中包括国家药品监督管理局中国药品审评中心认定的突破性疗法和优先审评认定; Breakthrough Therapy  Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA PRIority MEdicines (PRIME)) scheme; and named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED).

Sanofi Alliance
In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads development and manufacturing activities, and Sanofi leads commercialisation activities and records revenue. The two companies share costs and profits in all territories except the US. 澳门葡京网赌游戏从该协议中获得的收入在公司财务报表中报告为联盟收入和合作收入.

Following a revision 到澳门葡京网赌游戏公司与尼希米单抗在美国的开发和商业化的利润分享安排, Sanofi and Sobi, Sobi has entered into a direct relationship with Sanofi, replacing the previous participation agreement with AstraZeneca entered into in November 2018.

Beyfortus will be co-promoted by AstraZeneca and Sanofi in Japan.

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, 澳门葡京网赌游戏在100多个国家开展业务，其创新药物被全球数百万患者使用. Please visit dalova.net and follow the Company on social media @AstraZeneca.

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