A Randomized, Double-blind, Multicenter Study to Evaluate the Efficacy and Safety of ALX 0171 Versus Placebo, in Addition to Standard of Care, in Adults Who Have Undergone Hematopoietic Stem Cell Transplantation and Present With a Respiratory Syncytial Virus Respiratory Tract Infection

The primary objective of the study is to evaluate the antiviral effect and safety of inhaled ALX-0171 in adults diagnosed with respiratory syncytial virus (RSV) respiratory tract infection after hematopoietic stem cell transplantation (HSCT).
The secondary objective is to assess the clinical activity, pharmacokinetics (PK), virology, and immunogenicity of inhaled ALX 0171 in adults diagnosed with RSV respiratory tract infection after HSCT.

开始日期2019-02-01

申办/合作机构

Ablynx NV

NCT03418571

/ Terminated临床2期

A Randomized, Double-blind, Multicenter, Multiple-dose Study of ALX-0171 Versus Placebo Along With Standard of Care in Japanese Infants and Young Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection

This was a randomized, double-blind, multicenter, Phase II study (NCT03418571) designed to support the selection of an optimal dose of inhaled ALX-0171 for further clinical development, taking ethnicity into consideration.
Based on the results of the Phase IIb dose-ranging study ALX0171-C201 (RESPIRE), the Sponsor decided to discontinue ALX-0171 development in infants and to early terminate the ALX0171-C203 study.

开始日期2018-03-01

申办/合作机构

Ablynx NV

NCT02979431

/ Completed临床2期

A Randomized, Double-blind, Placebo-controlled, Multicenter Dose Ranging Study of ALX-0171 in Infants and Young Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection

The primary objective is to evaluate the anti-viral effect and safety of different doses of inhaled ALX-0171 in subjects hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection (RSV LRTI). The secondary objective is to evaluate the clinical activity, pharmacokinetic (PK) properties, pharmacodynamic (PD) effect and immunogenicity of different doses of inhaled ALX-0171.

开始日期2017-01-11

申办/合作机构

Ablynx NV

100 项与 ALX-0171 相关的临床结果

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100 项与 ALX-0171 相关的转化医学

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100 项与 ALX-0171 相关的专利（医药）

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项与 ALX-0171 相关的文献（医药）

2021-02-01·British Journal of Pharmacology

Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities

Review

作者: Rastegar, Mostafa ; Samadizadeh, Saeed ; Besteman, Sjanna ; Bont, Louis ; Tahamtan, Alireza ; Salimi, Vahid

Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS‐5806, ALX‐0171 and ALS‐8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.

2021-01-01·The Lancet. Respiratory medicine1区 · 医学

Nebulised ALX-0171 for respiratory syncytial virus lower respiratory tract infection in hospitalised children: a double-blind, randomised, placebo-controlled, phase 2b trial

1区 · 医学

Article

作者: Ashkenazi, Shai ; Oberdorfer, Peninnah ; Cunningham, Steve ; Toh, Teck Hock ; Piedra, Pedra A ; Martinon-Torres, Federico ; Salamanca de la Cueva, Ignacio ; Bene, Zsolt ; Warachit, Boonyarat ; Repko, Miroslav ; Goldbart, Aviv ; Fleurinck, Carmen ; Sablan, Benjamin, Junior ; Nikolova, Olga ; Kolosa, Nadezda ; Khaw, Poh Guan ; Martinón-Torres, Federico ; Piedra, Pedro A ; Rodrigo Gonzalo de Liria, Carlos ; Chakarova, Petranka ; Verhulst, Stijn ; Gacs, Éva ; Kalocsai, Krisztina ; Ivkovic-Jurekovic, Irena ; Turkalj, Mirjana ; Skalova, Sylva ; Kljaic Bukvic, Blazenka ; Kovacs, Lajos ; Brackeva, Benedicte ; Bosheva, Miroslava ; Szymanski, Henryk ; Puthanakit, Thanyawee ; Matthijs, Inge ; De Bruyne, Jessie Anne ; Vogelberg, Christian ; Cicak, Biserka ; Madarasi, Anna ; Wu Hupat, Elba ; Bentur, Lea ; Dombrecht, Evelyne ; SIPL, Mirna ; Mesaric Antoncic, Natasa ; Tesovic, Goran ; Gardovska, Dace ; Teeratakulpisarn, Jamaree ; Detalle, Laurent ; Tan, Kah Kee ; Novak, Zoltan ; Dosev, Svilen ; Goetghebuer, Tessa ; Cedena Romero, María Pilar ; Alberto, Edison ; Kralinsky, Karol ; Monteagudo Montesinos, Emilio ; Mesa Monsalve, Juan ; de Leon, Anjanette ; Horneff, Gerd ; Proesmans, Marijke

BACKGROUND:

Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection, with a high global health burden. There are no effective treatments available. ALX-0171 is a novel trivalent Nanobody with antiviral properties against RSV. We aimed to assess the safety and antiviral activity of nebulised ALX-0171 in children admitted to hospital with RSV lower respiratory tract infection.

METHODS:

This double-blind, randomised, placebo-controlled, phase 2b trial was done in 50 hospital paediatric departments across 16 countries. Previously healthy children aged between 28 days to younger than 24 months who were admitted to hospital with RSV acute severe lower respiratory tract infection were randomly assigned in three sequential safety cohorts (3:1) to receive nebulised ALX-0171 (cohort 1 received 3 mg/kg, cohort 2 received 6 mg/kg, and cohort 3 received 9 mg/kg) or placebo once daily for 3 days using web-based randomisation in the sequential safety part (first block size 12, subsequently four). In a parallel part of the study, participants (cohort 4) were randomly assigned (parallel 1:1:1:1) to receive nebulised ALX-0171 3 mg/kg, 6 mg/kg, 9 mg/kg, or placebo (blocks of eight by restricted randomisation). Study drug masking was by two consecutive nebulisations (each either ALX-0171 or placebo) depending on assigned treatment group. The primary outcome was to evaluate time for the RSV viral load to drop to below quantifiable limit, measured by plaque assay on mid-turbinate nasal swabs. Safety, clinical efficacy, pharmacokinetics, viral load by RT-qPCR, and immunogenicity were secondary outcomes. Analysis, including of the primary outcome, was by modified intention to treat (participants receiving at least one dose of study drug as assigned), and safety was assessed in all children who received at least one administration of study drug, as treated. This trial is registered with EudraCT, 2016-001651-49.

FINDINGS:

Between Jan 10, 2017, and April 26, 2018, 175 children (median age 4·8 months [IQR 2·0-10·8]), received at least one dose of study drug (45 received 3 mg/kg of ALX-0171, 43 received 6 mg/kg of ALX-0171, 45 received 9 mg/kg of ALX-0171, and 42 received placebo; the modified intention-to-treat population) commencing at a mean 3·3 days (SD 1·1) from symptom onset. Median time for the viral load to drop to below quantifiable limit on plaque assay was significantly faster for the 3 mg/kg group (median 14·2 h [IQR 5·0-28·0]), 6 mg/kg group (5·1 h [4·7-28·5]), and 9 mg/kg group (5·1 h [4·6-5·9]) than the placebo group (46·1 h [25·2-116·7]; hazard ratio [HR] all ALX-0171 groups vs placebo 2·6 [1·7-3·9]; p<0·0001). Median time for the viral load to drop below quantification limit with RT-qPCR was 95·9 h (IQR 26·7 to not estimable) for the placebo group (n=35) versus 49·4 h (25·1 to 351·4) for all ALX-0171 groups (n=118). Clinical outcomes were not improved by ALX-0171 compared with placebo, with no difference in time to clinical response (oxygen saturation >92% for 4 h in room air and adequate oral feeding) in ALX-0171 groups and the placebo group (median 43·8 h [IQR 21·7-68·5] vs 47·9 h [22·5-76·4]; HR 1·1 [95% CI 0·8-1·6]) or change in the global severity score from baseline to 5 h post-dose on day 2 (-4 [IQR -6 to -2] vs -4 [-6 to -1]; difference in least-squares mean -0·45 [95% CI -1·39 to 0·49]). Serum concentrations of ALX-0171 on day 2 exceeded the concentration estimated to give full RSV neutralisation in the lung at 6 mg/kg and 9 mg/kg doses. Treatment-emergent antidrug antibodies were detected at day 14 in 46 (34%) of 135 patients who received ALX-0171 and ten (26%) of 39 patients who received placebo. Serious adverse events were reported in five (13%) of 40 children in the placebo group and ten (7%) of 135 children in all ALX-0171 groups, leading to study drug discontinuation in three children (two in the 3 mg/kg group and one in the 6 mg/kg group). 13 of 15 serious adverse events (three of four in the 3 mg/kg group, two of three in the 6 mg/kg group, three of three in the 9 mg/kg group, and five of five in the placebo group) were related to worsening respiratory status, and none were considered to be related to the study drug.

INTERPRETATION:

Antivirals against RSV might be unable to improve clinical course once RSV lower respiratory tract infection is established. Future studies of RSV antivirals should focus on earlier intervention and more precise measurement of objective outcomes before the onset of significant lower respiratory tract inflammation.

FUNDING:

Ablynx, a Sanofi Company.

2017-01-01·Pharmacology & therapeutics

Nanobodies® † †Nanobody is a registered trademark of Ablynx NV. as inhaled biotherapeutics for lung diseases

Review

作者: de Fougerolles, Antonin ; Van Heeke, Gino ; Detalle, Laurent ; De Brabandere, Veronique ; Allosery, Koen ; De Smedt, Tim

Local pulmonary delivery of biotherapeutics may offer advantages for the treatment of lung diseases. Delivery of the therapeutic entity directly to the lung has the potential for a rapid onset of action, reduced systemic exposure and the need for a lower dose, as well as needleless administration. However, formulation of a protein for inhaled delivery is challenging and requires proteins with favorable biophysical properties suitable to withstand the forces associated with formulation, delivery, and inhalation devices. Nanobodies are the smallest functional fragments derived from a naturally occurring heavy chain-only immunoglobulin. They are highly soluble, stable, and show biophysical characteristics that are particularly well suited for pulmonary delivery. This paper highlights a number of clinical and preclinical studies on antibodies delivered via the pulmonary route and describes the advantages of using Nanobodies for inhaled delivery to the lung. The latter is illustrated by the specific example of ALX-0171, a Nanobody in clinical development for the treatment of respiratory syncytial virus (RSV) infections.

项与 ALX-0171 相关的新闻（医药）

2025-11-08

·今日头条

一文读懂纳米抗体：从结构优势到临床应用的全能生物制剂

纳米抗体（Nanobodies, Nbs）作为源于骆驼科动物和鲨鱼重链抗体（HCAbs）的单域可变区（VHH），是目前已知最小的功能性抗原结合单位。自 1993 年被发现以来，凭借 15kDa 的微小分子量、高稳定性、强组织穿透性等独特优势，已成为生物医学领域增长最快的生物制剂类别之一。从基础研究到临床应用，纳米抗体凭借灵活的工程化潜力和多元给药方式，正彻底改变生物制剂的研发格局。本文将系统拆解纳米抗体的核心特性、制备技术、临床应用与未来趋势，助你全面掌握这一 “全能生物工具”。一、核心定义与结构优势：微小身躯的强大能力纳米抗体是重链抗体的可变区片段（VHH），仅由单一结构域构成，尺寸约 4nm，是传统单克隆抗体（150kDa）的十分之一。其结构优势源于独特的序列与构象设计：亲水性与稳定性突出：FR2 区的疏水氨基酸被亲水氨基酸（Phe37、Glu44、Arg45、Gly47）替代，确保良好水溶性；同时含非经典二硫键，可在极端 pH（2-12）和高温（90℃）下保持活性。抗原结合精准高效：CDR3 区平均长度达 14 个氨基酸，比人类 IgG 的 CDRH3 长 3 个残基，可形成深入抗原凹槽的 “凸起结构”，甚至结合传统抗体难以触及的隐藏表位。工程化潜力巨大：单体结构简单，可轻松构建二价、三价多聚体，或与药物、荧光素、酶等分子偶联，实现多功能改造。二、制备与筛选技术：从文库到高活性抗体的高效转化纳米抗体的制备核心是 “文库构建 - 展示筛选 - 优化改造” 的标准化流程，技术成熟且高通量： 1. 文库构建三大来源免疫库：通过抗原免疫羊驼（免疫周期 6-8 周），从 B 淋巴细胞中克隆 VHH 基因，亲和力高但依赖动物免疫。天然库：源于未免疫骆驼科动物的 B 细胞，可筛选自身抗原、毒性抗原抗体，无需免疫但亲和力较低。合成库：人工设计 VHH 基因序列，结合 AI 工具（如 RFdiffusion）构建，无需动物实验，开发周期可缩短至 7 天。 2. 四大主流展示筛选平台噬菌体展示：以 M13 噬菌体为载体，通过固相 / 液相淘选（2-3 轮）富集高特异性克隆，适合大规模文库筛选（库容可达 10¹⁰）。酵母展示：将 VHH 基因与酵母表面蛋白融合，通过流式分选（FACS）高通量筛选高亲和力克隆，适配亲和力成熟。核糖体展示：无细胞体外展示系统，形成 “mRNA - 核糖体 - 蛋白质” 三元复合物，适合毒性蛋白筛选。细菌展示：将 VHH 与细菌表面蛋白（如 Lpp-OmpA）融合，通过磁珠分选（MACS）快速获得阳性克隆，兼顾筛选与催化应用。 3. 关键优化步骤人源化改造：通过 CDR 移植或序列优化，将非人源序列占比降至 5% 以下，降低免疫原性，目前已开发 Llamanade 等开源工具实现高效改造。亲和力成熟：针对 CDR3 区进行定点突变或易错 PCR 构建突变库，结合酵母展示筛选，亲和力可提升 10-100 倍。三、核心临床应用：覆盖多疾病领域的治疗潜力纳米抗体凭借精准靶向性和灵活改造能力，已在抗病毒、抗癌、自身免疫病等领域展现出显著疗效，多款候选药物进入临床试验： 1. 抗病毒治疗针对 SARS-CoV-2：开发靶向刺突蛋白 RBD 的三价纳米抗体，中和活性比单体提升 2000 倍，可有效应对变异株逃逸。针对 RSV：三价纳米抗体 ALX-0171 对 RSV A/B 亚型的效力优于临床药物帕利珠单抗，雾化给药安全性良好。其他病毒：针对流感、MERS-CoV、HIV 等的多价纳米抗体已进入临床前研究，部分展现出广谱中和活性。 2. 癌症免疫治疗 CAR-T 细胞疗法：纳米抗体作为抗原识别域，构建的 CAR-T 细胞已用于治疗 T-ALL、多发性骨髓瘤，3 个月缓解率达 75%。靶向治疗：双价 / 三价纳米抗体（如靶向 PD-L1/HER2、CD19/CD20）可增强肿瘤结合特异性，偶联化疗药物（如 MMAE）后实现精准杀伤。诊断成像：⁶⁸Ga 标记的 HER2 纳米抗体可快速实现肿瘤 PET 成像，注射后 1 小时即可获得清晰信号，肿瘤 / 背景比达 8:1。 3. 自身免疫病与血液疾病首个上市纳米抗体药物 Caplacizumab（抗 vWF 二聚体），用于治疗血栓性血小板减少性紫癜，疗效显著。针对 IL-17A/IL-17F 的异源三聚体纳米抗体 Sonelokimab，在银屑病 2b 期临床试验中响应率达 76.5%。 4. 其他领域抗菌治疗：靶向细菌毒力因子（如大肠杆菌志贺毒素）的纳米抗体，可特异性中和毒素，减少肠道菌群破坏。基因治疗：修饰腺相关病毒（AAV）载体，提升基因递送的靶向效率（如针对 CD4+ T 细胞的靶向递送效率提升 500 倍）。神经疾病：通过血脑屏障穿透技术，靶向 β- 淀粉样蛋白的纳米抗体可减少阿尔茨海默病小鼠脑内 Aβ 沉积达 60%。四、结构优化与药代动力学改善：突破临床应用瓶颈 1. 多价构建体设计通过柔性连接子（如 [GGGGS] n）、Fc 融合或病毒样颗粒（VLPs）组装，构建二价、三价甚至四价纳米抗体，可实现：亲和力提升（多价效应使亲和力增强 10-100 倍）；多靶点同时靶向（如同时阻断 PD-L1 和 CTLA-4）；延长半衰期（Fc 融合后半衰期从 2 小时延长至数天）。 2. 半衰期延长策略融合人血清白蛋白（HSA）或抗 HSA 纳米抗体，半衰期可延长至 1-2 周； PEG 修饰或脂质体封装，减少肾脏清除，提升体内稳定性； Fc 片段融合，借助 FcRn 循环实现长效循环。五、灵活给药途径：适配多元临床场景纳米抗体的稳定性与小尺寸使其适配多种给药方式，突破传统生物制剂的给药限制：静脉注射：适用于系统性疾病（如血液癌、自身免疫病），结合半衰期延长策略可减少给药频次。口服给药：超稳定纳米抗体可抵抗胃肠道消化环境，用于治疗肠道细菌感染（如 ETEC、轮状病毒感染）。吸入给药：雾化纳米抗体可直接作用于肺部，用于治疗 RSV、新冠病毒引起的呼吸道感染。细胞内给药：与细胞穿透肽（CPP）偶联，可进入细胞内靶向 STAT3 等胞内靶点，治疗三阴性乳腺癌。血脑屏障穿透：通过吸附介导的转胞吞或受体介导（如转铁蛋白受体靶向），实现中枢神经系统疾病治疗（如阿尔茨海默病）。六、人源化与生物安全：临床转化的核心保障纳米抗体与人类重链可变区（VHs）的序列同源性高达 80%，天然免疫原性较低。通过人源化改造（如 Llamanade 工具），可将其与人源框架的同一性提升至 95% 以上，进一步降低免疫风险。临床试验数据显示，纳米抗体类药物的抗药物抗体反应发生率低，对疗效影响微乎其微，安全性良好。总结与未来展望纳米抗体凭借 “小尺寸、高稳定性、强穿透性、易改造” 的核心优势，已成为生物制药领域的 “全能选手”。从抗病毒、抗癌到神经疾病治疗，从诊断成像到基因递送，其应用场景持续拓展。未来，随着 AI 辅助设计（如 AlphaFold2 结构预测）、新型递送系统（如工程细菌、细胞外囊泡）的融合，纳米抗体将进一步突破 “不可成药” 靶点的限制，为精准医疗带来更多创新方案。

临床研究

2024-04-24

·精准药物

第一批吃到螃蟹的药企

第一批开悟的药企，已率先享受RSV药物的时代红利。作为RSV药物的商业化元年，2023年有2款RSV疫苗和1款预防抗体药物合计斩获30亿美元销售额。随着市场竞争大幕缓缓拉开，更多药企持续开悟中。01国产不再“静悄悄”就中国市场而言，RSV药物赛道可谓是“蓝海中的蓝海”。目前，全球已获批的3款RSV药物，仅赛诺菲/阿斯利康的Beyfortus（尼塞韦单抗）于今年1月在中国上市，而GSK的Arexvy尚处于Ⅰ期临床，预计2026年实现商业化落地。尽管国内市场尚处于萌芽阶段，但潜力巨大。据灼识咨询数据，到2030年，中国RSV药物市场规模预计增至15亿美元，年复合增长率高达75.8%，远超全球同期增速（21.4%）。其中，针对儿童的RSV药物预计约占整个中国RSV药物市场的89.4%。这无疑吸引了众多国产企业布局，包括艾棣维欣、三叶草生物、沃森生物、艾美疫苗、智飞生物等，多数技术路线为已验证成药性的重组蛋白和mRNA。图片来源：中航证券研报进度最快的是艾棣维欣重组蛋白亚单位疫苗ADV110（BARS13），针对60-80岁老年人的II期临床试验，以及针对18-45岁成人的I期临床试验，均显示出良好的安全性、耐受性和免疫原性。三叶草生物基于其独有的Trimer-Tag（蛋白质三聚体化）疫苗技术平台开发的二价重组蛋白RSV候选疫苗SCB-1019，在针对18-59岁成人的I期试验中取得了积极初步数据。另外，处于临床早期阶段的还有康乐卫士、康泰生物布局的重组蛋白疫苗，以及百克生物布局的重组亚单位疫苗。mRNA疫苗方面，艾美疫苗、沃森生物/蓝鹬生物、石药集团和嘉晨西海等均已布局，目前处于临床早期阶段。值得一提的是，智飞生物与GSK于去年10月签订了在中国独家销售带状疱疹疫苗Shingrix的合作，同时还就后者的RSV疫苗Arexvy达成初步合作意向。除此以外，也有一些国产企业选择布局RSV预防药物。例如，爱科百发的RSV抗病毒特效药AK0529已向国家药监局递交上市申请，用于治疗婴幼儿、成人患者中RSV感染，有望成为全球首个获批的特效抗RSV病毒感染的临床药品；智翔金泰研发的重组RSV单抗GR2102，于今年2月获批临床，拟用于预防RSV感染。02全球争夺“大蛋糕”据不完全统计，目前全球有近70条在研RSV预防管线，涉及技术路线包括减毒活疫苗、亚单位疫苗、mRNA疫苗和针对不同病毒蛋白的重组载体候选疫苗，参与者不乏强生、默沙东等MNC巨头。其中，Moderna的mRNA-1345进展最快，对60岁以上老人效果显著，目前已申请在欧盟、瑞士、澳大利亚和美国等多地上市，并开展了针对儿科人群的临床试验。格外值得一提的是，已拥有RSV预防药物的阿斯利康，也顺势打入了RSV疫苗赛道：于2023年底斥资11亿美元溢价收购Icosavax，后者的核心产品IVX-A12是一种针对RSV和人偏肺病毒（hMPV）的潜在FIC的VLP组合候选疫苗，已被FDA授予针对60岁以上成人的快速通道资格，可与Synagis和Beyfortus形成互补，覆盖更多人群，且即将开展Ⅲ期临床试验。除技术创新外，一些企业还选择开发疫苗联合疗法。例如，近日GSK启动了RSV重组蛋白疫苗+新冠mRNA疫苗联合免疫的三期临床试验；Moderna也布局了一款流感/新冠/RSV三联mRNA疫苗mRNA-1230，目前处于临床前阶段。RSV预防药物的在研管线也不在少数，包括默沙东的clesrovimab、珠海泰诺麦博TNM001和赛诺菲的gontivimab等，均已处于临床Ⅱ期及以上阶段。从上述管线的进度不难看出，未来几年RSV药物的市场竞争将进入白热化阶段。全球RSV抗体管线丰富图片来源：开源证券研报由于RSV可感染广泛人群，扩大适用年龄范围成为推动RSV疫苗增长的关键。这点与HPV疫苗类似。默沙东的九价HPV疫苗之所以能爆卖，正是由于扩龄策略，将适用人群从16-26岁拓展至9-45岁适龄女性，使得潜在消费者基数大幅增加，市场空间实现了翻倍。除了老年人，RSV疫苗的适用人群还在持续拓展。今年1月底，欧盟已受理GSK的Arexvy扩龄至50-59岁成人的上市申请，预计今年下半年可获批上市。只是很可惜，Arexvy针对婴幼儿和孕妇的临床试验均未成功。另一边，辉瑞的Abrysvo也在扩龄：去年8月获得FDA批准新增胎龄32-36周孕妇适应症，以保护新生儿免受RSV感染。而且，Abrysvo针对18-59岁人群的III期研究已经成功，即将申请上市，同时正在开展针对2-17岁高危儿童及青少年的Ⅲ期临床试验。可见，无论GSK还是辉瑞，都在想方设法攻克儿童人群，尤其5岁以下婴幼儿。毕竟，该年龄段是RSV的最核心易感人群，市场前景更佳。据灼识咨询数据显示，针对儿童的RSV药物预计2030年将增至117亿美元，将占全球RSV药物市场的91.1%。基于此，不少药企布局了儿童RSV疫苗，包括赛诺菲的鼻喷减毒活疫苗LID/ΔM2-2/1030s（Ⅲ期，预计2026年提交上市申请）、BlueLake（蓝湖生物）的BLB-201（Ⅱ期）等。值得一提的是，赛诺菲的LID/ΔM2-2/1030s可以保护新生儿在第二个RSV流行季（次年4月-次年9月）不受感染，而与阿斯利康联合研发的Beyfortus，可保护新生儿在第一个RSV流行季（当年10月-次年3月）不受感染，可谓进行了全方位的布局。图片来源：民生证券研报03百亿美元赛道作为新晋明星赛道，RSV疫苗市场需求大、增长潜力足，被誉为“下一个HPV疫苗”。呼吸道合胞病毒（RSV）感染范围广泛，具有明显的季节性，尤其在秋末初冬时高发，对所有年龄段的人群都构成威胁，特别是婴幼儿、成年免疫缺陷者和老年人等高危人群。根据WHO统计数据显示，RSV每年导致全球约6400万儿童感染、36万成人入院。针对RSV感染的治疗，主要分为主动免疫（RSV疫苗）和被动免疫（RSV预防药物）两种治疗手段。1998年，诞生了全球首款RSV预防药物，MedImmune公司（后被阿斯利康收购）研发的Synagis（帕利珠单抗）获FDA批准上市，用于预防早产儿RSV引起的下呼吸道疾病。但由于价格昂贵、覆盖病患群体小（仅在美国获批用于治疗早产儿），且需每月注射一次，直到上市后的第10年，Synagis才跻身“重磅炸弹药物”行列。近两年，RSV预防药物迎来了重大突破：由阿斯利康和赛诺菲联合开发的Beyfortus（尼塞韦单抗），分别于2022年、2023年获欧盟、FDA批准上市，用于预防婴幼儿RSV引起的下呼吸道疾病。图片来源：平安证券研报相较之下，RSV疫苗的研发之路更加坎坷，耗时60多年才终于迎来曙光。2023年5月，葛兰素史克（GSK）的Arexvy、辉瑞的二价RSV疫苗Abrysvo相继获FDA批准上市，用于预防60岁及以上人群由RSV引起的下呼吸道疾病。至此，2023年成为了RSV药物的商业化元年，且销售表现不俗。其中，Arexvy仅销售7个月便大卖15.66亿美元，Abrysvo在6个月的时间实现销售额8.9亿美元，Beyfortus的营收也达到了5.98亿美元。GSK预测，Arexvy销售峰值将超过30亿英镑，彰显RSV疫苗市场的巨大潜力。由于感染广泛、疾病负担重、市场尚处蓝海，RSV药物市场具备百亿美元级别的潜力。据灼识咨询研究数据显示，RSV药物全球整体市场规模预计到2030年将增长至128亿美元。参考资料：1.各家公司的财报、公告、官微2.《11亿美元AZ入新局，与辉瑞、GSK开启“三国杀”？RSV赛道谁是国内第一玩家？》，E药经理人，2023-12-163.平安证券、民生证券、开源证券、中航证券研报声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 金银花转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

疫苗临床1期信使RNA临床2期

2019-02-07

·BioSpace

Sanofi Cuts a Whopping 38 R&D Programs to Refocus on Cancer, Immunology, and Rare Diseases

ricochet64 / Shutterstock Thirteen of those were development programs, the remaining 25 research-stage. In September, the company indicated it was on a cost-cutting program, planning to save 1.5 billion euros this year. Of the programs it is dumping, the most prominent is a mid-phase drug for respiratory syncytial virus (RSV), ALX-0171. ricochet64 / Shutterstock.com What a difference a year makes. In January 2018, Paris-based Sanofi marked the start of the year by acquiring Waltham, Mass.-based Bioverativ for $11.6 billion and Ghent, Belgium-based Ablynx for $4.8 billion. A year later, at its fourth-quarter and annual report today, Sanofi announced it has killed 38 R&D programs, prioritizing oncology, immunology, rare disease and rare blood disorders. Thirteen of those were development programs, the remaining 25 research-stage. In September, the company indicated it was on a cost-cutting program, planning to save 1.5 billion euros this year. “In the fourth quarter, we continued the momentum of the previous quarter and we delivered 5 percent full-year business EPS growth, at the high end of our guidance,” stated Olivier Brandicourt, Sanofi’s chief executive officer. “In 2018, we executed on important launches including Dupixent, Libtayo and Cablivi, as the headwinds from our U.S. LoEs (loss of exclusivity) began to moderate. Additionally, the acquisitions of Bioverativ and Ablynx provided the foundation to build a leading Rare Blood Disorder franchise and to enhance our biologic discovery capabilities. As we enter 2019, our focus remains on delivering our business priorities and transforming Sanofi to address the evolving business dynamics facing our industry.” Just yesterday, the U.S. Food and Drug Administration (FDA) approved Cablivi (caplacizumab-yhdp) in combination with plasma exchange and immunosuppression to treat acquired thrombotic thrombocytopenic purpura (aTTP) in adults. It is the first FDA approved drug for aTTP. Cablivi was a drug Sanofi picked up when it acquired Ablynx. Of the programs it is dumping, the most prominent is a mid-phase drug for respiratory syncytial virus (RSV), ALX-0171. It is also a program it picked up with Ablynx. The company has also ended a collaboration with MyoKardia , which is behind several of the abandoned programs, and last year the company ended a deal with Immune Design that was related to the TLR4 peanut allergy program. Total net sales for the quarter were 8.997 billion euros, with full-year sales of 34.463 billion euros. The largest area of growth for the quarter and the year was Specialty Care, with sales of 2.328 billion euros, an increase of 35.2 percent, and 8.269 billion euros for the year, an improvement of 29 percent. The worst area, however, was Generics. For the quarter, Generics sales were 270 million euros, a decrease of 33.8 percent. For the year, Generics sales were 1.490 billion euros, a decrease of 9.8 percent. The hottest drugs in its Pharmaceutical franchise were Cerdelga, for Gaucher’s disease, which brought in 44 million euros for the quarter, an increase of 33.3 percent, and 159 million euros for the year, an increase of 31 percent. This was followed by Aldurazyme, for Hurler and Hurler-Scheie diseases, which brought in 54 million euros for the quarter, up 16.7 percent, and 206 million euros for the year, an increase of 6.7 percent. The company’s multiple sclerosis franchise, the drugs Aubagio and Lemtrada, brought in 542 million euros for the quarter and 2.049 billion euros for the year. The company’s Diabetes franchise, like much of the diabetes market, was down. Total Diabetes sales for the quarter was 1.375 billion euros, down 10.5 percent, and 5.472 billion euros for the year, down 10.4 percent. The company also updated its R&D strategy, increasing its focus on Specialty Care areas, oncology, immunology, rare disease and rare blood disease, while also remaining committed to vaccines. Sanofi noted that, “Since 2017, the number of R&D programs in these areas has increased significantly, and they now represent over 90 percent of Sanofi’s clinical portfolio.” Aside from the 38 programs it cut, the company says it potentially will be able to submit nine new drugs and 25 additional indications to regulators over 2019 to 2022.

上市批准并购生物类似药

100 项与 ALX-0171 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16179

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
下呼吸道感染	临床2期	澳大利亚	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	比利时	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	保加利亚	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	爱沙尼亚	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	匈牙利	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	以色列	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	拉脱维亚	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	马来西亚	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	菲律宾	Ablynx NV	2014-12-01
下呼吸道感染	临床2期	波兰	Ablynx NV	2014-12-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02979431 (Respire, CTgov)	临床2期	呼吸道合胞体病毒感染	180	Placebo (Placebo)	壓糧鹽簾膚網築鏇衊鹽(顧糧鹽構構觸獵鬱獵艱) = 繭鑰蓋醖鬱網窪鏇蓋蓋齋鹽範顧餘醖鹽遞壓製 (衊積顧獵鬱願齋製醖範, 齋鏇積憲製獵廠夢憲簾 ~ 衊廠餘簾廠廠願獵選膚) 更多	-	2019-10-18
				ALX-0171 3.0 mg/kg (ALX-0171 3.0 mg/kg)	壓糧鹽簾膚網築鏇衊鹽(顧糧鹽構構觸獵鬱獵艱) = 顧觸齋築淵膚積蓋醖範齋鹽範顧餘醖鹽遞壓製 (衊積顧獵鬱願齋製醖範, 鑰窪遞鑰網齋網獵遞鑰 ~ 膚膚醖範壓襯餘遞積蓋) 更多
NCT03418571 (CTgov)	临床2期	呼吸道合胞体病毒感染	15	ALX-0171 1.5 mg/kg (ALX-0171 1.5 mg/kg)	鹽鹹鬱繭鏇鬱選獵窪願 = 顧選願鬱遞顧鹽鬱願選膚廠憲淵簾廠獵蓋顧淵 (積襯構糧獵製願窪糧觸, 蓋衊夢艱製構鹽選選廠 ~ 鏇糧衊衊鹽鹹窪夢繭衊) 更多	-	2019-07-15
				Placebo (Placebo)	鹽鹹鬱繭鏇鬱選獵窪願 = 壓憲糧鏇襯構鏇齋廠繭膚廠憲淵簾廠獵蓋顧淵 (積襯構糧獵製願窪糧觸, 糧鹽窪淵窪構衊憲齋選 ~ 遞壓製願積襯鬱淵淵醖) 更多