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日前，启明创投投资企业爱科百发宣布国际儿童青少年健康领域的顶级期刊《柳叶刀·儿童青少年健康》（The Lancet Child & Adolescent Health）在线发表了首个RSV特异性抗病毒药物齐瑞索韦（Ziresovir）的3期临床研究成果，题为“Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up”。这是继该项3期临床研究结果在2024年9月发表于《新英格兰医学杂志》后，再次登上全球知名医学期刊。

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RSV：亟待解决的医疗需求

呼吸道合胞病毒（RSV）感染在婴幼儿健康领域，堪称“隐匿的杀手”，是婴幼儿住院和死亡的最重要因素之一。在全球范围内，每年有大量婴幼儿因RSV感染而遭受病痛折磨，给家庭和社会带来沉重的负担。目前，针对RSV感染的治疗手段十分有限，主要以对症辅助性支持治疗为主，缺乏特效抗病毒药物。这意味着在面对RSV感染时，医生们常常只能通过缓解症状来帮助患儿，无法从根本上对抗病毒。尤其是6个月以下婴儿，因免疫系统及呼吸道发育不成熟，感染后易发展为重症，住院率和重症监护需求显著高于其他年龄段。因此，针对高危婴儿群体RSV感染的有效疗法开发迫在眉睫。基于以上背景，齐瑞索韦的3期研究首次在6个月以下的住院婴儿中验证了齐瑞索韦的临床疗效，并揭示了其减少再发喘息和哮喘的长期获益。

该研究是多中心、随机、双盲、安慰剂对照的3期临床试验，在中国28家医院的30个中心开展。研究分为两部分：第一部分（Part 1）评估安全性；第二部分（Part 2）验证疗效与安全性。患者按2:1比例随机接受齐瑞索韦（根据体重给药：10、20、40 mg，每日两次）或安慰剂治疗5天，并完成24个月的随访。本研究为年龄在6个月以下患者的亚组分析和24个月的随访结果。

核心研究结果显示：

1. 疗效显著 

毛细支气管炎显著改善：治疗组第3天毛细支气管炎临床评分（Wang bronchiolitis clinical score，WBCS）较基线下降3.5分（安慰剂组为2.2分），差异达54.5%（p<0.001），且呼吸频率、喘息、呼吸肌凹陷等分项评分均显著优于安慰剂（p<0.05）。 

病毒载量快速下降：治疗组第5天病毒载量较基线降低2.51 log₁₀拷贝/mL（安慰剂组为1.87 log₁₀拷贝/mL），相比安慰剂组多降0.64 log₁₀拷贝/mL（p=0.024），提示齐瑞索韦具有明显的抗病毒效果。 

症状缓解加速：治疗组喘息缓解时间（HR=1.53, p=0.021）与呼吸肌凹陷缓解时间（HR=1.49, p=0.018）显著缩短，住院时长与氧疗需求虽无统计学差异，但呈现改善趋势。

2. 长期安全性良好

安全性良好：治疗组与安慰剂组药物相关不良事件（TEAEs）发生率分别为18%和11%，未发生严重药物相关不良事件或死亡病例。  

3. 喘息风险降低

喘息和哮喘发生率显著下降：治疗组年化喘息发生率较安慰剂组降低3.6倍（治疗组与安慰剂组分别为0.18%与0.65%, p=0.0048）；喘息发作次数减少2.6倍（治疗组与安慰剂组分别为1.2次与3.1次）；治疗组哮喘诊断率（3%）低于安慰剂组（5%）。研究结果提示早期抗病毒治疗可对儿童远期呼吸道健康（如反复喘息、哮喘）产生保护效应。

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RSV治疗新纪元

当前RSV感染治疗以控制症状为主，齐瑞索韦的疗效为临床提供了首个特异性抗病毒药物选择。尤其对于6个月以下的婴儿，由于其重症风险高、免疫力低，选择齐瑞索韦快速降低病毒载量可有效遏制病情进展。同时本试验首次通过长期随访证明，齐瑞索韦可降低喘息发生的相关风险，其机制可能与病毒载量控制及炎症反应减轻有关。这一发现不仅拓展了抗病毒药物的临床价值，也为RSV相关慢性呼吸疾病的防治策略提供了新思路。

今年3月，在巴西举行的第13届全球RSV学术双年会上，爱科百发CEO邬征博士通过大会主题报告展示了这一原创成果，引起了国际同行的广泛关注和认可。齐瑞索韦在国际大会的一次次亮相，展现了爱科百发和中国临床专家在儿童药研发领域的创新实力，从实验室到世界舞台的跨越，为破解全球呼吸道疾病难题提供了“中国创新药”。

首都医科大学附属北京儿童医院院长倪鑫教授表示：“RSV感染作为儿科领域亟待攻克的难题，因长期缺乏特异性治疗手段，不仅严重威胁婴幼儿生命健康，更加剧了儿科医疗资源的运行负担。本研究作为全球首个覆盖6月龄以下RSV感染婴儿的3期临床试验，成功填补了针对这一高危人群特异性治疗方案的循证空白，为构建RSV全病程管理体系提供了关键证据。这一成果的临床转化将改变既往被动支持治疗的困境，推动RSV诊疗进入精准治疗的新时代。继去年3期核心数据荣登《新英格兰医学杂志》后，本研究深度分析再度获《柳叶刀·儿童青少年健康》收录，充分体现了国际学术界对中国原创临床研究的认可。我为团队取得的这一成就感到由衷的自豪，并期待齐瑞索韦能早日获批上市，让中国和全球RSV患儿获益于这一开创性新药。”

The Lancet Child & Adolescent Health Publishes Phase 3 Trial and 24-Month Follow-Up Results of Ziresovir for RSV in Infants Under 6 Months

The Lancet Child & Adolescent Health, a leading international journal in pediatric and adolescent medicine, has published the Phase 3 clinical trial results of ziresovir, a novel RSV-targeted antiviral drug developed by Shanghai Ark Biopharmaceutical Ltd, a portfolio company of Qiming Venture Partners. 

The article, titled "Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up," presents detailed subgroup analysis of infants under six months of age, following the primary results published in The New England Journal of Medicine in September 2024.

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RSV: An Urgent Unmet Medical Need

Respiratory syncytial virus (RSV) is a leading cause of hospitalization and mortality in children under six years old. With millions of cases annually worldwide, especially among infants under six months, RSV imposes a significant burden on families and healthcare systems. Current treatments are limited to symptomatic and supportive care, with no approved direct-acting antiviral therapies available.

Ziresovir's Phase 3 results mark a significant milestone, representing the first clinical validation of an antiviral's efficacy in hospitalized infants ≤6 months, and demonstrating long-term benefits in reducing recurrent wheezing and asthma.

Study Design

This multicenter, randomized, double-blind, placebo-controlled Phase 3 trial was conducted at 30 sites in 28 hospitals across China. The trial included two parts: Part 1 assessed safety and pharmacokinetics and Part 2 evaluated clinical efficacy and antiviral effects.

Infants were randomized in a 2:1 ratio to receive ziresovir or placebo for five days, with a 24-month follow-up. The latest publication focuses on infants aged six months or younger.

Key Findings

1. Significant Efficacy

Improved Bronchiolitis Symptoms: By Day 3, ziresovir-treated infants had a 3.5-point reduction in Wang Bronchiolitis Clinical Score (WBCS), compared to 2.2 points in the placebo group—a 54.5% difference (p<0.001). Improvements in respiratory rate, wheezing, and retractions were also statistically significant (p<0.05).

Rapid Viral Load Reduction: By Day 5, viral load decreased by 2.51 log₁₀ copies/mL in the treatment group, versus 1.87 log₁₀ copies/mL in the placebo group (p=0.024), confirming ziresovir's antiviral activity.

Faster Symptom Relief: Time to wheezing resolution (HR=1.53, p=0.021) and retraction relief (HR=1.49, p=0.018) were shorter in the treatment group. Hospital stay and oxygen use showed a reduction trend, though not statistically significant.

2. Long-Term Safety and Respiratory Health Benefits

Favorable Safety Profile: Treatment-emergent adverse events (TEAEs) occurred in 18% of the treatment group vs. 11% in placebo. No drug-related severe adverse events or deaths were reported.

Reduced Risk of Recurrent Wheezing and Asthma: Wheezing incidence was 3.6 times lower in the treatment group (0.18% vs. 0.65%, p=0.0048); wheezing episodes were reduced by 2.6 times (1.2 vs. 3.1 episodes); asthma rates were also lower (3% vs. 5%).

These long-term benefits suggest early antiviral intervention may reduce the risk of chronic respiratory conditions.

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A New Era in RSV Treatment

Unlike existing RSV treatments focused solely on symptom relief, ziresovir is the first RSV-targeted antiviral therapy with demonstrated clinical efficacy in infants under six months—those most at risk of severe complications. These findings introduce a new therapeutic paradigm for RSV treatment and prevention of long-term sequelae.

The results were presented by Dr. Jim Wu, CEO of ArkBio, at the 13th International RSV Symposium in Brazil, receiving recognition from the global RSV research community.

Prof. Xin Ni, principal investigator of the Airflo study and professor at Beijing Children's Hospital, Capital Medical University, commented: "This pivotal Phase 3 trial provides the first solid evidence of an effective antiviral treatment for RSV in high-risk infants. Following our initial publication in The New England Journal of Medicine, this deeper analysis in infants under six months published in The Lancet Child & Adolescent Health further validates ziresovir's safety, efficacy, and long-term benefit. We are proud of our team's commitment and look forward to bringing this drug to patients in China and worldwide."