预约演示

更新于：2026-09-07

Dengue vaccine tetravalent(Sanofi)

更新于：2026-09-07

概要

概要

基本信息

药物类型

预防性疫苗、多价疫苗

别名

Chimeric Yellow Fever Dengue Virus Serotype 1 (Live, Attenuated)/Chimeric Yellow Fever Dengue Virus Serotype 2 (Live, Attenuated)/Chimeric Yellow Fever Dengue Virus Serotype 3 (Live, Attenuated)/Chimeric Yellow Fever Dengue Virus Serotype 4 (Live, Attenuated)、ChimeriVax、ChimeriVax Tetravalent Dengue Vaccine

+ [13]

靶点-

作用方式

刺激剂

作用机制

免疫刺激剂

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Sanofi-Aventis Australia Pty Ltd.Sanofi Pasteur, Inc.Sanofi-Aventis, Inc.

非在研机构

Sanofi Pasteur SA

Sanofi Winthrop Industrie SA

Sanofi

权益机构-

最高研发阶段批准上市

首次获批日期

澳大利亚 (2017-07-20),

登革热

最高研发阶段(中国)-

特殊审评-

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关联

项与 Dengue vaccine tetravalent(Sanofi) 相关的临床试验

CTRI/2023/10/058630

/ Active, not recruiting临床3期

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (Live, Attenuated) (TDV) Administered Subcutaneously to Healthy Subjects Aged 4 to 60 Years in India - NIL

开始日期2024-02-12

申办/合作机构

Takeda Vaccines, Inc.

NCT04486638

/ RecruitingN/A

Dengvaxia US Pregnancy Registry: A Surveillance Study to Assess the Safety of Dengvaxia Among Exposed Pregnant Women and Their Offsprings (DNG00044)

The primary objective of this study is to assess maternal, obstetrical, pregnancy, and neonatal and infant outcomes among women and their offspring(s) vaccinated with Dengvaxia during their pregnancy

开始日期2023-01-01

申办/合作机构

Sanofi Pasteur SA

NCT04023708

/ CompletedN/A

A Pregnancy Registry to Evaluate the Safety of Dengue Vaccine Among Inadvertently Exposed Pregnant Women and Their Offsprings (DNG16)

Primary Objective:
To evaluate the safety of CYD-TDV in pregnant women and their offsprings inadvertently exposed during pregnancy or up to 30 days preceding their last menstrual period (LMP) with regards to maternal, pregnancy, birth, neonatal and infant outcomes. Specifically, the frequency/rates of these outcomes will be: (i) described, and (ii) compared with population-level background incidence rates prior to the introduction of CYD-TDV immunization (i.e., external unvaccinated comparator).
Secondary Objective:
To describe:
* the characteristics of women exposed to CYD-TDV during pregnancy or up to 30 days before the LMP
* the characteristics of CYD-TDV pregnancy exposure with regards to number of doses, dose intervals, and trimester of exposure.

开始日期2022-03-11

申办/合作机构

Sanofi Pasteur SA

100 项与 Dengue vaccine tetravalent(Sanofi) 相关的临床结果

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100 项与 Dengue vaccine tetravalent(Sanofi) 相关的转化医学

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100 项与 Dengue vaccine tetravalent(Sanofi) 相关的专利（医药）

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331

项与 Dengue vaccine tetravalent(Sanofi) 相关的文献（医药）

2026-10-01·ACTA TROPICA

Neutralizing dengue antibodies after 10 years of the chimeric yellow fever tetravalent dengue vaccine (CYD-TDV) and dengue antibody cross-reactivity with SARS-CoV-2 in Indonesia

Article

作者: Alam, Anggraini ; Satari, Hindra Irawan ; Karyanti, Mulya Rahma ; Hadinegoro, Sri Rezeki ; Sasmono, R Tedjo ; Widyahening, Indah Suci ; Munasir, Zakiudin

BACKGROUND:

Dengue endemic countries were affected by the spread of COVID-19. In 2011, Indonesia participated in a multi-center phase III clinical trial of chimeric yellow fever tetravalent dengue vaccine (CYD-TDV). This study evaluates neutralizing dengue antibodies of CYD-TDV after 10 years during COVID-19 pandemic.

OBJECTIVE:

To assess neutralizing antibody against all four-dengue virus (DENV) serotypes and dengue incidence in individuals who received CYD-TDV after 10 years immunization in Indonesia. Additionally, to compare SARS-CoV-2 neutralizing antibody titers and COVID-19 incidence between dengue-vaccinated and non-vaccinated groups.

METHODS:

This study was conducted across five healthcare centers in Jakarta (June-December 2022) involving 419 participants (207 dengue-vaccinated, 212 non-vaccinated). A cross-sectional study in subset of 79 dengue-vaccinated and 80 non-vaccinated participants were measured neutralizing antibodies against DENV and SARS-CoV-2, respectively. Simultaneously, all participants were given questionnaires to assess dengue and COVID-19 history.

RESULTS:

In adolescents (12-17 years), CYD-TDV recipients had significantly higher neutralizing antibody titers against DENV-1, DENV-2, and DENV-4, but not DENV-3. While, no significant differences were observed in adults (≥18 years) in both groups. Dengue incidence was similar between dengue-vaccinated (4.8%) and non-vaccinated (5.1%) groups. The SARS-CoV-2 neutralizing antibody levels were not significantly different between groups. However, incidence of hospitalized COVID-19 were higher in the dengue-vaccinated group.

CONCLUSION:

After a decade, CYD-TDV induced higher neutralizing antibody levels significantly for DENV-1, DENV-2, and DENV-4, but not for DENV-3 in adolescents but not in adults. The SARS-CoV-2 neutralizing antibody levels were comparable between groups, However, COVID-19 hospitalizations were more frequent in dengue-vaccinated group.

2026-08-01·VACCINE

Beyond neutralization: A comprehensive framework for evaluating humoral immunity induced by a live-attenuated tetravalent dengue vaccine

Article

作者: Dean, Hansi ; Sharma, Mayuri ; Nascimento, Eduardo J M ; Gottardo, Raphael ; Tricou, Vianney

OBJECTIVE:

Dengue incidence is increasing worldwide. TAK-003, a live-attenuated tetravalent dengue vaccine, is licensed in several countries. Its safety, efficacy, and immunogenicity have been extensively studied and provided the roadmap for recommendations and implementation. Per WHO guidelines, the primary immunogenicity endpoint in dengue vaccine clinical trials is neutralizing antibody (NAb) titers. However, there is no established immunological correlate of protection, and dengue virus (DENV) elicits a broad range of antibody responses. This study assessed statistical and experimental methods to evaluate a wide range of antibody responses to TAK-003 as a framework for evaluating vaccine immunological signatures that may correlate with protection from dengue infection and/or disease.

METHODS:

Responses were assessed by the following immunoassays: microneutralization assay, DENV total binding IgG ELISA, anti-dengue complement antibody assay, anti-dengue non-structural protein 1 (NS1) IgG ELISA, and anti-dengue IgG avidity assay. Samples from TAK-003 vaccinated/placebo participants from several trials were tested. Results were compared for assay performance and the impact of baseline serostatus, serotype, and age on vaccine-elicited responses. Correlation analyses assessed relationships among variables. Principal component analyses (PCA) evaluated data complexity.

RESULTS:

Vaccination elicited responses to all four DENV serotypes in each assay. The magnitude of vaccine-induced responses was higher in baseline seropositive participants, but vaccine effect was stronger in baseline seronegative participants. Baseline seronegative participants had comparable DENV total binding IgG concentrations, anti-dengue IgG avidity, and anti-dengue complement antibody titer responses across all serotypes. MNT₅₀ NAb and anti-dengue NS1 IgG responses varied by serotype. Modest to low correlations across parameters suggest that the different assays measure non-redundant vaccine-induced humoral immune responses. The major source of response variability was post-vaccination time, followed by serotype.

CONCLUSION:

TAK-003 vaccination elicited multiple non-overlapping, unique humoral immune responses. Data support including parameters in addition to NAbs to better assess vaccine-induced humoral responses.

CLINICALTRIALS:

govregistration:NCT01511250, NCT02302066, NCT02747927, NCT03423173.

2026-08-01·VACCINE

Characterization of vaccine viremia, attenuation reversion, and safety: Combined results from the TAK-003 dengue vaccine clinical development program

Article

作者: Low, Jenny G ; Tricou, Vianney ; Rauscher, Martina ; Roubinis, Nicholas ; Reynales, Humberto ; Moss, Kelley J ; Livengood, Jill ; Borja-Tabora, Charissa ; Sharma, Mayuri ; Pang, Hang ; Sirivichayakul, Chukiat ; Saez-Llorens, Xavier ; Kosalaraksa, Pope ; Mandaric, Sanja ; Messer, William B ; Biswal, Shibadas

Live-attenuated vaccines can replicate for a transient period post-vaccination and may be associated with symptoms resembling natural infection. The tetravalent dengue vaccine, TAK-003, has undergone extensive preclinical assessment to investigate vaccine RNAemia, viremia, genetic stability, and transmissibility. Here, we investigated the presence of vaccine RNAemia, attenuation loci reversions, and their association with viral-syndrome-like adverse events (AEs) in participants throughout the clinical development program. TAK-003 RNA positive serum samples were evaluated for viral replication and sequenced for reversions. Safety data (solicited AEs within 7/14 days; unsolicited AEs within 28 days) were assessed from a pooled phase 1/2 trial analysis. Participants who experienced febrile illness within 30 days post vaccination in the pivotal phase 3 DEN-301 trial and the phase 2 DEN-313 trial were tested for RNAemia and evaluated for AEs. TAK-003 RNAemia was detected in 441/805 (54.8%) of vaccinees (seronegative: 67.0%; seropositive: 33.0%) in the pooled analysis and in 39 participants with febrile illness from the DEN-301/DEN-313 trials (from 1022 febrile illnesses investigated). RNAemia peaked during the second week post-vaccination and mostly occurred after first dose. Although all four dengue virus (DENV) components were detected, RNAemia was most commonly due to DENV-2. 69 single locus reversions were detected; AEs reported in participants with reversions were generally non-serious, and not indicative of increased symptom severity. Pain at injection site (without RNAemia = 42.0%; RNAemia = 46.8%) and headache (without RNAemia = 36.6%; RNAemia = 37.6%) were the most frequently reported solicited AEs. Incidences of pain, erythema, rash, arthralgia, and fatigue were higher in participants with RNAemia. The incidence of unsolicited AEs was higher in participants with RNAemia (62.4%) than without (52.0%). In the DEN-301/DEN-313 analysis, participants with febrile illness showed a similar pattern of symptoms with and without RNAemia. The presence of RNAemia was associated with transient, mild-to-moderate symptoms, resembling natural infection, which were also observed in the absence of RNAemia.

项与 Dengue vaccine tetravalent(Sanofi) 相关的新闻（医药）

2026-08-14

·被忽视疾病药物研发倡议组织

登革热：从“补漏”到“止漏”的范式转变

据估计，全球每年发生3.9亿例登革热感染，2024年的登革热疫情更是破纪录。当疫苗接种登上舞台，登革热防控能否从“补漏”转向“止漏”？本文盘点Dengvaxia、Qdenga和Butantan-DV三大疫苗突破，看医学创新如何为面临登革热感染风险的人群筑起防线。 01 //日益严峻的全球健康威胁// 登革热被世界卫生组织（WHO）列为“全球十大健康威胁”之一，并且仍然是全球最普遍的虫媒病毒感染。登革热病毒（DENV）属黄病毒科，通过埃及伊蚊和白纹伊蚊传播，它们在热带和亚热带城市环境中大量滋生。在过去三十年中，由于气候变化、城市化、全球化和病媒控制不足，登革热发病率急剧上升，使得中低收入国家的卫生保健系统负担过重。据估计，全球每年发生3.9亿例登革热感染，目前生活在100多个国家的超过全球一半的人口面临感染风险。 2024年，登革热疫情创下历史纪录，全球报告病例超1460万例，死亡病例逾12000例。美洲区域报告了约1300万例病例，其中巴西的病例数超过1000万例。值得注意的是，登革热正持续向传统流行区以外扩散。欧洲部分地区（包括法国、意大利和西班牙）已报告本地传播病例，三国合计308例。 02 //免疫发病机制与血浆渗漏// 登革热的严重程度由四种病毒血清型（DENV-1至DENV-4）与宿主免疫应答的相互作用决定。原发性感染仅对本次感染的血清型产生终身免疫。若再次感染不同血清型，初次感染产生的异型抗体可能与病毒结合却无法将其中和，形成免疫复合物，进而促进病毒侵入单核细胞与巨噬细胞。这一现象即为抗体依赖性增强（ADE），其会促进病毒复制和炎症介质释放，最终导致内皮功能紊乱与毛细血管渗漏——这是重症登革热的标志。在人群层面，优势血清型的转换往往会增加重症继发性感染的风险，预示疫情的暴发。在有症状的登革热感染者中，大约3-5%会发展为重症登革热。该疾病病程通常分为三个阶段：以急性发热为特征的发热期；发生在退热后24-48小时，且以血浆渗漏、血浓缩和低血容量性休克风险为特征的极期；以及恢复期，在此期间患者病情持续好转。根据世界卫生组织2009年指南，登革热分为非重症（无预警征、有预警征）和重症登革热。预警指征包括：腹痛、持续呕吐、昏睡、第三间隙积液、黏膜出血、肝脏肿大，以及红细胞压积上升伴血小板计数迅速下降。超过90%的重症病例可归因于由血浆渗漏导致的低血容量性休克、腹水或胸腔积液，而较小比例的病例则源于严重出血或器官功能障碍。 03 //预防：从病媒控制到疫苗接种// 病媒控制传统上是登革热防控的基石，包括清除蚊虫滋生地和在疫情期间进行有针对性的熏雾灭蚊。创新方法正在涌现，特别是释放携带沃尔巴克氏菌（Wolbachia）的埃及伊蚊，这与马来西亚选定热点地区的登革热发病率降低60%以上有关。疫苗接种代表着一项重大突破。首个获批的登革热疫苗Dengvaxia（CYD-TDV）因在血清阴性者中存在安全隐患而应用受限——对此类人群而言，接种疫苗会模拟原发性感染过程，从而在后续发生自然感染时增加重症风险，这与抗体依赖性增强（ADE）现象一致。相比之下，Qdenga（TAK-003）作为一种四价减毒活疫苗，针对病毒学确诊登革热显示出61.2%的保护效力，对登革热相关住院显示出84.1%的保护效力，且在血清阴性接种者中未发现重症风险增加的证据。该疫苗于2024年2月在马来西亚获有条件批准，采用两剂方案、间隔三个月，可供四岁及以上人群在私立医疗机构接种，无论其血清状态如何。近期，由巴西布坦坦研究所（Butantan Institute）开发的单剂量疫苗Butantan-DV显示出约65%的总体效力，针对重症登革热或有预警指征的登革热显示出80.5%的保护效力。该疫苗已于2026年初被纳入巴西国家免疫规划。本文译自登革热联盟（Dengue Alliance）专家Lim Chee Loon医生在Malaysian Medical Association Journal发表的文章“Dengue: A Paradigm Shift From Refilling A Leaking Bucket To Stopping The Leak”。 Dr Steven Lim Chee Loon 是马来西亚霹雳州怡保Raja Permaisuri Bainun医院的传染病专科顾问医师，同时担任马来西亚感染控制和传染病学会（Malaysian Society of Infection Control and Infectious Diseases, MyICID）主席。关于DNDi 被忽视疾病药物研发倡议组织（DNDi）是一个以病患需求为出发点的非营利性药物研发组织。DNDi主要为被忽视的疾病患者研发新的治疗方法，其中包括昏睡病、南美锥虫病、利什曼病、淋巴丝虫病、足菌肿、儿童艾滋病/艾滋病以及丙型肝炎的治疗方法。DNDi同时也在协调ANTICOV临床试验，为非洲的轻度至中度新冠肺炎（COVID-19）患者寻找治疗方法。自2003年成立以来，DNDi迄今已交付了13种全新的治疗方案，其中包括用于治疗利什曼病的新药物组合、两种固定剂量的抗疟药，首次成功研发的新化学实体药物非昔硝唑（fexinidazole）用于治疗昏睡病，以及通过南南合作研发的丙肝药物拉维达韦（ravidasvir），旨在为全球丙肝患者提供可负担的药物选择。 *点击下方图片，了解更多有关DNDi的介绍。

2026-07-30

·Firstwordpharma

Biopharma bites: Scribe sets IPO terms, Takeda's dengue shot OKed in India

Scribe shoots for $100M IPOTakeda gets India's first dengue vaccine approvalScribe shoots for $100M IPOScribe Therapeutics has set terms for its proposed public debut, according to a Monday securities filing. The company plans to sell 7.2 million shares at a range of $13 to $15; at the midpoint, it would raise $100.1 million and command a fully diluted market value of $235 million.Alongside its IPO, the biotech will pocket an additional $7.5 million in a concurrent private placement from Sanofi. Scribe has two deals with the French pharma, with the most recent covering use of CRISPR XE technologies for the development of in vivo therapies, including for sickle cell disease.Scribe is engineering purpose-built in vivo CRISPR technologies, with its lead asset STX-1150 under development for the treatment of hypercholesterolaemia. The company joined the IPO queue in early July and since then, a half-dozen other biotechs have lined up behind it.-Elizabeth EatonTakeda gets India's first dengue vaccine approvalTakeda has secured approval in India for its live-attenuated dengue vaccine Qdenga, making it the first vaccine greenlit in the country to prevent the mosquito-borne illness. Formerly TAK-003, the vaccine was approved in the EU in late 2022, but remains unavailable in the US after Takeda withdrew its FDA application in 2023 following discussions over "aspects of data collection."The vaccine is indicated for children and adults ages four through 60 years and is designed to protect against all four dengue virus serotypes without requiring recipients to undergo pre-vaccination testing. That could give it a leg up on Sanofi's ⁠Dengvaxia, which isn't approved in India and is only recommended for people with prior dengue infection given concerns that those without previous exposure to the virus may face a greater risk of severe disease.Qdenga demonstrated 80.2% efficacy against confirmed dengue one year after the second dose and 90.4% efficacy against dengue-related hospitalisations after 18 months in a Phase III TIDES trial. Takeda partnered with Indian vaccine manufacturer Biological E in 2024 to expand production capacity.-Anna Bratulic

上市批准临床3期疫苗IPO临床结果

2026-07-17

·wukong的小筑

Sanofi（赛诺菲）MIDD技术演变观察（2010–2026）

一、概述 Sanofi（赛诺菲，法国）是全球制药行业中在代谢疾病、免疫炎症和疫苗三大领域同时拥有深厚MIDD积累的少数MNC之一。基于对Sanofi公开发表的MIDD相关论文的系统分析，本数据库覆盖2010–2026年，共收录780篇独立MIDD论文，覆盖12个MIDD子方向。 Sanofi的MIDD布局呈现"代谢-免疫双核驱动，疫苗差异化竞争"的鲜明特征。与多数MNC以肿瘤学为MIDD主战场不同，Sanofi将糖尿病/代谢领域的定量科学传统与免疫学领域的新一代生物制剂开发深度融合，同时在疫苗这一独特赛道上建立了从临床免疫原性建模到公共卫生影响评估的全链条MIDD能力。二、代谢与内分泌MIDD——从胰岛素PKPD到GLP-1组合创新的定量科学糖尿病和代谢疾病是Sanofi历史最悠久、MIDD积累最深厚的治疗领域。从第一代重组胰岛素到新一代基础胰岛素类似物Gla-300（Toujeo），再到GLP-1受体激动剂与固定比例复方（iGlarLixi），Sanofi在代谢领域的MIDD实践呈现出一条清晰的"从PKPD表征到临床剂量优化到组合创新"的技术演进路径。2.1 胰岛素Glargine U300（Gla-300）：新一代基础胰岛素的PKPD创新 Insulin glargine 300 U/mL（Gla-300，商品名Toujeo）是Sanofi在代谢领域最具代表性的MIDD驱动产品。与传统的glargine 100 U/mL（Gla-100，Lantus）相比，Gla-300通过制剂创新实现了更平坦、更持久的药代动力学/药效学（PK/PD）曲线，从而在临床实践中带来更低的低血糖风险。 Gla-300的PKPD表征：[^1]是理解其临床优势的起点。这项发表于Diabetes Care的随机、双盲、交叉研究在30名1型糖尿病患者中应用了正糖钳夹技术（euglycemic clamp），在稳态条件下对Gla-300和Gla-100进行了为期36小时的PK/PD对比。结果显示，Gla-300的葡萄糖输注率（GIR）曲线相比Gla-100更加平坦，作用持续时间超过30小时，且PK暴露的日内变异显著降低。这项工作的价值在于：它不仅是制剂开发后的PK/PD验证，更直接为后续EDITION系列III期临床试验的剂量选择提供了定量基础——Gla-300的平坦PK/PD曲线意味着可以使用更高剂量而不会增加低血糖风险。 EDITION系列III期试验：Gla-300的临床开发以EDITION系列研究为核心。EDITION 1[^2]在2型糖尿病患者中比较了Gla-300与Gla-100联合餐时胰岛素的效果，证明了Gla-300在非劣效降糖的同时，夜间低血糖发生率显著降低。这篇论文覆盖PKPD和ExR两个方向，其核心贡献在于将"PK/PD优势→临床结局改善"的因果链通过暴露-反应分析进行了定量验证。患者级荟萃分析：[^3]将EDITION 1、2、3三项研究的个体患者数据进行了整合分析，这是Sanofi在代谢领域MIDD方法论的一个标志性工作。通过患者级数据建模，研究者不仅确认了Gla-300在不同基线胰岛素使用水平患者中的一致性降糖效果，更重要的是量化了低血糖风险降低的幅度——这为临床实践中"什么样的患者能从Gla-300获益最大"提供了定量答案。 1型糖尿病中的验证：[^4]在1型糖尿病患者中开展的EDITION 4研究进一步验证了Gla-300的PK/PD优势在胰岛素绝对缺乏人群中的适用性。该研究发表于Diabetes Care，覆盖PKPD和ExR两个方向，完成了Gla-300从2型到1型糖尿病的全人群覆盖。2.2 iGlarLixi——固定比例复方的MIDD整合创新 LixiLan（即iGlarLixi，商品名Soliqua）是Sanofi将基础胰岛素glargine与GLP-1受体激动剂lixisenatide以固定比例组合的创新产品，代表了代谢领域"组合创新"的MIDD范式。 LixiLan的III期临床：[^5]发表于Diabetes Care，证明了iGlarLixi相较于单独使用glargine或lixisenatide在降糖效果和体重影响方面的综合优势。这篇论文覆盖PKPD和ExR两个方向，其MIDD价值在于：在设计阶段即考虑了两种药物在PK/PD层面的互补性——glargine提供24小时基础胰岛素覆盖，lixisenatide提供餐后血糖控制和胃排空延缓——并通过暴露-反应分析验证了这种互补在临床终点上的体现。 Lixisenatide的临床前PKPD：[^6]发表于Regulatory Peptides，系统描述了lixisenatide作为GLP-1受体激动剂的药理特征——包括其对胰岛素分泌的葡萄糖依赖性刺激、对胃排空的延缓作用、以及对胰高血糖素分泌的抑制。这篇临床前DPM工作为后续的复方开发提供了机制性基础。2.3 Teplizumab——1型糖尿病的免疫干预MIDD Teplizumab（抗CD3单克隆抗体）代表了Sanofi在代谢领域从"替代治疗"到"疾病修饰"的战略拓展。Teplizumab是美国FDA批准的首个延缓1型糖尿病临床发病的药物。 Teplizumab在新诊断1型糖尿病中的III期试验：[^7]发表于NEJM，评估了teplizumab在新诊断1型糖尿病（stage 3）患者中保护β细胞功能的效果。该研究覆盖DPM方向，通过C肽水平的定量建模评估了β细胞功能保留程度，为"免疫干预改变疾病进程"的MIDD理念提供了临床验证。三、免疫与炎症MIDD——Dupilumab的全适应症精准免疫调节免疫与炎症是Sanofi近年来MIDD产出增长最快的领域，核心驱动力是Dupilumab（度普利尤单抗/Dupixent）——一款靶向IL-4受体α亚基的全人源单克隆抗体。Dupilumab通过同时阻断IL-4和IL-13信号通路，实现了对Th2型炎症的精准调控，其适应症从特应性皮炎扩展到哮喘、慢性鼻窦炎伴鼻息肉、嗜酸性食管炎，直至2024年获批COPD适应症——成为首个在这一领域展示疗效的生物制剂。这一全适应症拓展过程是MNC中"单一药物、多适应症MIDD"的教科书级案例。3.1 Dupilumab在特应性皮炎——从概念验证到精准药效 Dupilumab治疗中重度特应性皮炎的里程碑III期：[^8]发表于NEJM，是Dupilumab临床开发中具有里程碑意义的论文。这项随机、双盲、安慰剂对照研究首次在成人中重度特应性皮炎患者中证明了IL-4Rα阻断的临床疗效，覆盖PKPD和ExR两个方向。其MIDD价值在于：早期临床开发中即建立了"靶点占位→Th2细胞因子抑制→临床评分改善"的暴露-效应链，为后续所有适应症的剂量选择提供了定量框架。青少年特应性皮炎：[^9]发表于JAMA Dermatology，将Dupilumab的MIDD框架扩展至青少年人群。该研究覆盖PKPD和ExR两个方向，通过群体PK分析验证了青少年和成人在PK/PD特征上的可比性，避免了在青少年人群中开展独立的大规模剂量探索研究。 Dupilumab对皮肤微生物组的影响：[^10]发表于Journal of Investigative Dermatology，揭示了Dupilumab的一个意外但重要的药效学效应——IL-4Rα阻断不仅抑制Th2炎症，还通过恢复皮肤屏障功能减少了金黄色葡萄球菌（Staphylococcus aureus）的定植并增加了微生物多样性。这项DPM研究的方法论意义在于：它展示了MIDD如何从"靶点→临床终点"的传统框架扩展到"靶点→微环境→生态学终点"的多维分析，为理解Dupilumab的全面药效提供了新的维度。3.2 Dupilumab在哮喘——Th2炎症的精准分层 Dupilumab治疗未控制持续性哮喘的III期：[^11]发表于Lancet，是Dupilumab在呼吸领域的首个关键III期试验。该研究覆盖DPM方向，其核心MIDD贡献在于：通过基线嗜酸性粒细胞水平和呼出气一氧化氮（FeNO）等生物标志物的分层分析，识别了最可能从IL-4Rα阻断中获益的哮喘亚群——这一"标志物驱动的精准分层"策略成为后续所有Dupilumab呼吸适应症开发的模板。3.3 Dupilumab在COPD——Th2炎症新边疆的突破 Dupilumab治疗伴2型炎症的COPD：[^12]发表于NEJM，是2024年呼吸领域最具影响力的临床研究之一。该研究覆盖DPM方向，证明了Dupilumab在血嗜酸性粒细胞计数升高的COPD患者中显著减少急性加重。这一工作的MIDD意义重大：COPD传统上被认为是一种中性粒细胞驱动的疾病，Dupilumab的成功为"COPD中存在Th2炎症亚型"这一假说提供了临床验证，也展示了MIDD如何通过生物标志物分层（血嗜酸性粒细胞≥300 cells/μL）实现"老疾病、新靶点"的精准定位。3.4 Sarilumab——IL-6通路的定量阻断 Sarilumab（Kevzara）是Sanofi开发的抗IL-6Rα全人源单克隆抗体，在类风湿关节炎（RA）和COVID-19中展示了IL-6通路阻断的定量药理学。 MONARCH试验——Sarilumab vs Adalimumab头对头：[^13]发表于Annals of the Rheumatic Diseases，是Sarilumab在RA领域的关键III期研究。该研究覆盖ExR方向，通过头对头比较证明了IL-6R阻断在甲氨蝶呤不耐受或不充分应答患者中优于TNF-α阻断（adalimumab）。其MIDD价值在于：通过暴露-反应分析量化了Sarilumab在不同剂量水平下对DAS28-CRP评分的影响，为200mg q2w的推荐剂量提供了定量支持。 Sarilumab在COVID-19中的应用：[^14]发表于The Lancet Respiratory Medicine，评估了Sarilumab在重症/危重症COVID-19患者中的疗效和安全性。该研究覆盖PKPD和ExR两个方向，虽然最终结果未达到主要终点，但其MIDD实践展示了在紧急公共卫生事件中快速应用"机制导向的定量药理学框架"的能力——IL-6水平升高是COVID-19细胞因子风暴的核心特征，Sarilumab的靶点选择正是基于这一机制性假设。3.5 Rilzabrutinib——BTK抑制剂在皮肤免疫疾病中的拓展 Rilzabrutinib（SAR444671）是Sanofi开发的口服、可逆、共价BTK抑制剂，其适应症拓展体现了Sanofi在免疫学领域"从Th2到B细胞/肥大细胞"的技术演进。 Rilzabrutinib治疗慢性自发性荨麻疹：[^15]发表于JAMA Dermatology，评估了口服BTK抑制剂在抗组胺药难治性CSU中的疗效。该研究覆盖PKPD和ExR两个方向，其MIDD亮点在于：通过BTK靶点占位与临床瘙痒评分的PK/PD关联分析，为BTK抑制剂在肥大细胞驱动疾病中的剂量选择提供了定量基础——这是Sanofi在免疫学领域从"生物制剂"向"口服靶向小分子"拓展的MIDD新范式。3.6 Itepekimab——抗IL-33的COPD新靶点探索 Itepekimab是Sanofi开发的抗IL-33单克隆抗体，代表了Sanofi在"警报素"（alarmin）通路——IL-33/TSLP上游——的布局。 Itepekimab在COPD中的II期试验：[^16]发表于The Lancet Respiratory Medicine，该研究设计独特：首先通过遗传关联分析验证了IL-33通路基因变异与COPD风险的相关性，再通过随机对照试验评估了itepekimab在既往吸烟者中的临床疗效。该研究覆盖DPM方向，其MIDD方法论创新在于：将"遗传学验证→靶点确认→临床验证"的链条整合为单一的定量决策框架，为"警报素靶向治疗"在COPD中的应用提供了概念验证。四、心血管MIDD——PCSK9抑制剂的定量药理学 Alirocumab（阿利西尤单抗/Praluent）是Sanofi与Regeneron合作开发的PCSK9抑制剂，代表了心血管领域"从替代终点到临床结局"的MIDD范式。4.1 Alirocumab的临床前到临床PKPD桥接 Alirocumab的抗动脉粥样硬化作用：[^17]发表于Journal of Lipid Research，在APOE*3Leiden.CETP转基因小鼠模型中系统评估了alirocumab的抗动脉粥样硬化效果。该研究覆盖PKPD和ExR两个方向，其MIDD价值在于：通过"PCSK9抑制→LDL-C降低→斑块面积减少→斑块形态改善"的级联定量分析，为alirocumab在临床中的抗动脉粥样硬化作用提供了机制性证据。 Alirocumab对脂蛋白(a)的影响：[^18]发表于The American Journal of Cardiology，汇总了3项II期研究的数据，系统分析了alirocumab对Lp(a)水平的降低效果。该研究覆盖PKPD和ExR两个方向，发现alirocumab在降低LDL-C的同时显著降低Lp(a)——一个独立的心血管风险因子——这一发现为alirocumab的"多重脂质获益"提供了定量证据。4.2 ODYSSEY HoFH——纯合子家族性高胆固醇血症的挑战 ODYSSEY HoFH试验：[^19]发表于Journal of the American College of Cardiology，评估了alirocumab在纯合子家族性高胆固醇血症（HoFH）患者中的疗效。HoFH患者由于LDL受体功能严重缺陷，对传统降脂治疗反应极差。该研究覆盖PKPD和ExR两个方向，其MIDD贡献在于：通过"残余LDL受体活性→PCSK9抑制效应"的定量关系分析，为这一极端表型人群的个体化治疗提供了模型依据。五、神经科学MIDD——多发性硬化症的全病程定量 Sanofi在神经科学领域拥有从口服小分子到CNS穿透性BTK抑制剂的完整管线，在多发性硬化症（MS）的全病程管理中建立了系统的MIDD框架。5.1 Teriflunomide——从首次临床事件到疾病修饰 Teriflunomide（特立氟胺/Aubagio）是Sanofi开发的口服免疫调节剂，用于复发缓解型多发性硬化症（RRMS）。 TOPIC试验：[^20]发表于The Lancet Neurology，评估了teriflunomide在首次临床脱髓鞘事件（clinically isolated syndrome, CIS）患者中预防转化为临床确诊MS的效果。该研究覆盖PKPD和ExR两个方向，其MIDD价值在于：通过"暴露→淋巴细胞抑制→临床复发风险"的定量链，将teriflunomide的干预窗口从"已确诊MS"前移至"疾病最早期"——这是MS领域"早期干预改变疾病进程"理念的MIDD实践。5.2 Tolebrutinib——CNS穿透性BTK抑制剂的定量创新 Tolebrutinib是Sanofi开发的具有CNS穿透性的口服BTK抑制剂，其设计目标是解决MS中由小胶质细胞驱动的慢性神经炎症——这是传统免疫调节剂未能有效覆盖的病理通路。 Tolebrutinib在RRMS中的IIb期研究：[^21]发表于The Lancet Neurology，通过剂量-反应关系分析确定了tolebrutinib在减少新发脑MRI病灶方面的最优剂量。该研究覆盖PKPD和ExR两个方向，其MIDD创新在于：将"脑穿透性"作为关键的PK参数纳入剂量选择模型——tolebrutinib的CNS/血浆暴露比是剂量优化的核心约束条件，而非仅仅依赖血浆PK。 Tolebrutinib在非复发性继发进展型MS中的III期：[^22]发表于NEJM，是tolebrutinib最具突破性的临床研究。该研究覆盖DPM方向，证明了tolebrutinib在非复发性继发进展型MS（nrSPMS）中能够延缓残疾进展——这是目前唯一在此类患者中展示疗效的口服BTK抑制剂。其MIDD意义在于：nrSPMS以慢性神经炎症和神经退行性变为核心特征，传统免疫调节剂在该人群中效果有限，tolebrutinib通过CNS穿透性BTK抑制靶向小胶质细胞活化，代表了"机制导向的精准神经科学MIDD"。六、疫苗MIDD——从免疫原性到公共卫生影响的建模疫苗是Sanofi区别于其他MNC的独特领域。Sanofi的疫苗MIDD不仅涉及传统的免疫原性PK/PD分析，还扩展到了公共卫生影响建模和成本效益分析——这是其他MNC的MIDD实践中极少涉及的方向。6.1 登革热疫苗Dengvaxia——公共卫生建模的复杂挑战 Dengvaxia的长期安全性、公共卫生影响和成本效益：[^23]发表于PLoS Medicine，是Sanofi在疫苗MIDD领域最具方法论深度的论文之一。该研究覆盖CTS方向，构建了一个整合了"疫苗效力衰减→抗体依赖性增强（ADE）风险→血清型特异性保护"的数学模型，评估了Dengvaxia在不同传播强度地区的长期公共卫生影响。该研究的MIDD方法论价值在于处理了疫苗开发中罕见的"非线性风险"问题：Dengvaxia在血清阴性接种者中观察到的住院风险增加，要求模型不仅要预测"疫苗能预防多少病例"，还要预测"疫苗可能增加多少重症风险"，并且这两个预测都依赖于当地登革热传播强度、年龄结构和血清流行率。这种"获益-风险双轨建模"的复杂程度远超常规的疫苗效力预测模型。6.2 mRNA疫苗佐剂的免疫应答建模序列工程化mRNA疫苗的佐剂效应：[^24]发表于Journal of Translational Medicine，通过翻译组学分析比较了mRNA疫苗在人类和小鼠模型中的先天免疫应答。该研究覆盖DPM方向，其MIDD贡献在于：为mRNA疫苗的"翻译→先天免疫激活→适应性免疫"级联反应提供了定量描述，为mRNA疫苗的序列优化和佐剂设计提供了数据驱动的决策框架。七、罕见病MIDD——酶替代疗法的PopPK-QSP数字孪生 Sanofi在罕见病领域拥有从酶替代疗法（ERT）到小分子底物减少疗法的完整管线，其在Pompe病中的MIDD实践代表了"从传统PopPK到QSP数字孪生"的方法论前沿。7.1 Avalglucosidase Alfa——Pompe病的QSP数字孪生 Pompe病是一种由酸性α-葡萄糖苷酶（GAA）缺乏导致的进行性神经肌肉疾病，分为婴儿型（IOPD）和晚发型（LOPD）。Avalglucosidase alfa（AVAL，商品名Nexviazyme）是Sanofi开发的第二代ERT，旨在通过增强的M6P（甘露糖-6-磷酸）修饰提高肌肉靶向性。 QSP数字孪生方法：[^25]发表于Clinical Pharmacology and Therapeutics，是Sanofi在罕见病MIDD领域最具方法学创新性的论文。由于IOPD患者数量极少且表型异质性极高，传统临床试验设计面临严重挑战。Sanofi的团队开发了基于定量系统药理学（QSP）的"数字孪生"（digital twin）方法——通过整合患者特异性糖原积累速率、GAA酶活性、ERT药代动力学和肌肉功能数据，为每个虚拟患者构建个体化的疾病进展和治疗反应模型，以补充有限的临床试验数据。这一方法论的突破性在于：它从"群体平均"的PopPK范式转向了"个体化虚拟"的QSP范式，为罕见病药物开发中"样本量不足"的根本性挑战提供了一种数学解决方案。 Avalglucosidase Alfa的PopPK分析：[^26]发表于Journal of Pharmacokinetics and Pharmacodynamics，通过非线性混合效应模型建立了AVAL在LOPD患者中的群体药动学模型，并基于体重分层提出了儿童患者的替代给药方案。该研究覆盖PopPK和CTS两个方向，通过模拟40mg/kg q2w和20mg/kg q2w两种方案的暴露量分布，为基于体重阈值的剂量转换提供了定量依据。7.2 Venglustat——GBA相关神经退行性疾病的底物减少疗法 Venglustat是Sanofi开发的葡萄糖神经酰胺合成酶（GCS）抑制剂，通过减少葡萄糖神经酰胺的合成来治疗GBA突变相关的帕金森病和戈谢病。 Venglustat的临床前药理：[^27]发表于Scientific Reports，在GBA相关突触核蛋白病小鼠模型中证明了GCS抑制对α-突触核蛋白聚集和神经病理学的影响。该研究覆盖DPM方向，其MIDD价值在于：建立了"GBA突变→葡萄糖神经酰胺积累→α-突触核蛋白聚集→神经退行"的级联定量模型，为venglustat的临床剂量选择提供了从靶点抑制到病理学改善的完整证据链。八、肿瘤MIDD——剂量优化与生物标志物驱动的精准策略虽然肿瘤学并非Sanofi的MIDD主战场，但Sanofi在紫杉烷类化疗药（cabazitaxel）和CD38靶向免疫治疗（isatuximab）中的MIDD实践展示了"剂量优化"和"生物标志物驱动"两种核心方法论。8.1 Cabazitaxel——暴露-毒性平衡的剂量优化 Cabazitaxel（卡巴他赛/Jevtana）是Sanofi开发的第二代紫杉烷类化疗药，专门设计用于克服紫杉烷耐药。 PROSELICA III期——剂量优化：[^28]发表于Journal of Clinical Oncology，是cabazitaxel的MIDD代表性工作。该研究比较了20mg/m²和25mg/m²两种剂量方案在转移性去势抵抗性前列腺癌（mCRPC）中的疗效和安全性，覆盖PKPD和ExR两个方向。其核心MIDD贡献在于：通过暴露-反应分析证明了20mg/m²方案在维持生存获益的同时显著降低了血液学毒性风险，为"低剂量非劣效"的临床实践提供了定量决策依据。 Cabazitaxel的临床前PKPD：[^29]发表于Clinical Cancer Research，系统描述了cabazitaxel的临床前抗肿瘤活性——包括其对紫杉烷敏感和耐药细胞系的差异化作用、对纯化微管蛋白的亲和力、以及体内肿瘤模型的PK/PD关系。该研究覆盖PKPD和ExR两个方向，为cabazitaxel从实验室到临床的转化提供了完整的PKPD桥接。8.2 Isatuximab——CD38靶向的PKPD建模 Isatuximab（SAR650984，商品名Sarclisa）是Sanofi开发的抗CD38单克隆抗体，用于复发/难治性多发性骨髓瘤（RRMM）。 Isatuximab的疾病-药物相互作用PopPK：[^30]发表于CPT: Pharmacometrics & Systems Pharmacology，是Sanofi在大分子MIDD领域的方法论代表作。该研究发现了一个重要的药物-疾病相互作用：多发性骨髓瘤患者体内异常增高的"M蛋白"可能与治疗性IgG单克隆抗体竞争FcRn（新生儿Fc受体）介导的再循环通路，导致isatuximab的清除率随时间变化。这一发现解释了isatuximab在治疗初期清除较快、随M蛋白下降而清除减慢的PK特征，为给药间隔的优化提供了机制性解释。 Isatuximab的PK/PD建模与剂量选择：[^31]发表于同一期刊，通过将血清M蛋白浓度作为PD标志物纳入PK/PD数学模型，系统表征了isatuximab的暴露-疗效关系。该研究覆盖PKPD、CTS和ExR三个方向，其方法论贡献在于：将"肿瘤负荷标志物（M蛋白）→靶点介导的药物清除→暴露量→疗效"的闭环反馈整合为统一的数学框架，为isatuximab的剂量方案选择提供了完整的模型基础。8.3 Amcenestrant——Neural-ODE驱动的肿瘤动力学建模 Amcenestrant（SAR439859）是Sanofi开发的口服选择性雌激素受体降解剂（SERD），其MIDD实践代表了Sanofi在方法学前沿的探索。 DN-ODE模型：[^32]发表于Computers in Biology and Medicine，是Sanofi在肿瘤MIDD领域最具方法论创新性的论文。该研究提出了一种数据驱动的神经ODE（Neural Ordinary Differential Equation）建模方法，用于描述乳腺癌肿瘤动力学和预测无进展生存期（PFS）。与传统群体PK/PD模型相比，神经ODE方法能够从有限的患者数据中学习个体化的肿瘤生长-消退动力学，为"早期临床数据→个体化预测"的转化提供了一种新的计算框架。九、PBPK与转化科学 Sanofi在PBPK和转化科学领域的贡献虽然论文数量不及AZ或Roche，但在特定方向上有独特的深度。 PBPK模型资格认定与报告程序：[^33]发表于Clinical Pharmacology and Therapeutics，这篇由19家成员公司组成的Simcyp Consortium联合发表的共识文件，Sanofi是参与方之一。该论文建立了PBPK模型用于监管提交的标准化流程，是PBPK从"学术工具"升级为"监管科学基础设施"的里程碑工作。口服剂型体内性能的PBPK预测：[^34]发表于European Journal of Pharmaceutical Sciences，综述了PBPK模型在预测口服剂型体内性能方面的应用进展，覆盖药物溶出、肠道渗透和首过代谢等多个环节。该论文为Sanofi在小分子药物开发中应用PBPK进行制剂优化提供了方法论基础。位点特异性ADC糖基工程：[^35]发表于Bioconjugate Chemistry，描述了通过糖基工程实现位点特异性抗体-药物偶联（ADC）的方法。虽然该论文主要属于药物化学领域，但其对ADC的药代动力学均一性有直接影响——位点特异性偶联显著降低了ADC的PK变异度，为后续ADC的MIDD建模提供了更均一的PK输入。参考文献 [^1] PMID:25150159 — "New insulin glargine 300 Units·mL⁻¹ provides a more even activity profile and prolonged glycemic control at steady state..." Diabetes Care, 2015, 343次引用, MIDD-PKPD/ExR [^2] PMID:25078900 — "New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin..." Diabetes Care, 2014, 278次引用, MIDD-PKPD/ExR [^3] PMID:25929311 — "Patient-level meta-analysis of the EDITION 1, 2 and 3 studies..." Diabetes, Obesity and Metabolism, 2015, 202次引用, MIDD-PKPD/ExR [^4] PMID:26084341 — "New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 1 Diabetes..." Diabetes Care, 2015, 183次引用, MIDD-PKPD/ExR [^5] PMID:27650977 — "Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes..." Diabetes Care, 2016, 241次引用, MIDD-PKPD/ExR [^6] PMID:20570597 — "Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes." Regulatory Peptides, 2010, 147次引用, MIDD-DPM [^7] PMID:37861217 — "Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes." NEJM, 2023, 233次引用, MIDD-DPM [^8] PMID:25006719 — "Dupilumab treatment in adults with moderate-to-severe atopic dermatitis." NEJM, 2014, 1254次引用, MIDD-PKPD/ExR [^9] PMID:31693077 — "Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis..." JAMA Dermatology, 2020, 472次引用, MIDD-PKPD/ExR [^10] PMID:31252032 — "IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis." J Invest Dermatol, 2020, 199次引用, MIDD-DPM [^11] PMID:27130691 — "Dupilumab efficacy and safety in adults with uncontrolled persistent asthma..." Lancet, 2016, 817次引用, MIDD-DPM [^12] PMID:38767614 — "Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation." NEJM, 2024, 244次引用, MIDD-DPM [^13] PMID:27856432 — "Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis..." Ann Rheum Dis, 2017, 266次引用, MIDD-ExR [^14] PMID:33676590 — "Sarilumab in patients admitted to hospital with severe or critical COVID-19..." Lancet Respir Med, 2021, 211次引用, MIDD-PKPD/ExR [^15] PMID:40266575 — "Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria: The RILECSU Phase 2 Randomized Clinical Trial." JAMA Dermatology, 2025, 22次引用, MIDD-PKPD/ExR [^16] PMID:34302758 — "Safety and efficacy of itepekimab in patients with moderate-to-severe COPD..." Lancet Respir Med, 2021, 199次引用, MIDD-DPM [^17] PMID:25139399 — "Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin." J Lipid Res, 2014, 182次引用, MIDD-PKPD/ExR [^18] PMID:25060413 — "Effect of alirocumab, a monoclonal PCSK9 antibody, on lipoprotein(a) concentrations..." Am J Cardiol, 2014, 184次引用, MIDD-PKPD/ExR [^19] PMID:32646561 — "Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial." J Am Coll Cardiol, 2020, 151次引用, MIDD-PKPD/ExR [^20] PMID:25192851 — "Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC)..." Lancet Neurol, 2014, 271次引用, MIDD-PKPD/ExR [^21] PMID:34418400 — "Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis..." Lancet Neurol, 2021, 179次引用, MIDD-PKPD/ExR [^22] PMID:40202696 — "Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis." NEJM, 2025, 113次引用, MIDD-DPM [^23] PMID:27898668 — "The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine..." PLoS Med, 2016, 196次引用, MIDD-CTS [^24] PMID:28049494 — "Adjuvant effects of a sequence-engineered mRNA vaccine..." J Transl Med, 2017, 153次引用, MIDD-DPM [^25] PMID:39632463 — "Quantitative Systems Pharmacology-Based Digital Twins Approach Supplements Clinical Trial Data for Enzyme Replacement Therapy in Pompe Disease." Clin Pharmacol Ther, 2025, 11次引用, MIDD-QSP [^26] PMID:37535240 — "Population pharmacokinetic modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimens..." J Pharmacokinet Pharmacodyn, 2023, 5次引用, MIDD-PopPK/CTS [^27] PMID:34686711 — "Preclinical pharmacology of glucosylceramide synthase inhibitor venglustat in a GBA-related synucleinopathy model." Sci Rep, 2021, 27次引用, MIDD-DPM [^28] PMID:28809610 — "Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m²) and the Currently Approved Dose (25 mg/m²) in Postdocetaxel Patients..." J Clin Oncol, 2017, 247次引用, MIDD-PKPD/ExR [^29] PMID:23589177 — "Preclinical antitumor activity of cabazitaxel, a semisynthetic taxane active in taxane-resistant tumors." Clin Cancer Res, 2013, 199次引用, MIDD-PKPD/ExR [^30] PMID:33021075 — "Drug-Disease Interaction and Time-Dependent Population Pharmacokinetics of Isatuximab in Relapsed/Refractory Multiple Myeloma." CPT:PSP, 2020, 26次引用, MIDD-PopPK [^31] PMID:34185964 — "PK/PD modeling analysis for dosing regimen selection of isatuximab as single agent and in combination therapy..." CPT:PSP, 2021, 19次引用, MIDD-PKPD/CTS/ExR [^32] PMID:39089112 — "DN-ODE: Data-driven neural-ODE modeling for breast cancer tumor dynamics and progression-free survivals." Comput Biol Med, 2024, 15次引用, MIDD-PKPD/ExR [^33] PMID:29315504 — "Physiologically Based Pharmacokinetic Model Qualification and Reporting Procedures for Regulatory Submissions..." Clin Pharmacol Ther, 2018, 358次引用, MIDD-PBPK [^34] PMID:24060672 — "PBPK models for the prediction of in vivo performance of oral dosage forms." Eur J Pharm Sci, 2014, 284次引用, MIDD-PBPK [^35] PMID:24533768 — "Site-specific antibody-drug conjugation through glycoengineering." Bioconjug Chem, 2014, 210次引用, MIDD-PKPD/ExR

100 项与 Dengue vaccine tetravalent(Sanofi) 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D12227	-	J07BX	DB14764

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适应症	国家/地区	公司	日期
登革热	澳大利亚	Sanofi-Aventis Australia Pty Ltd.	2017-07-20

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适应症	最高研发状态	国家/地区	公司	日期
严重登革热	临床3期	澳大利亚	Sanofi Pasteur SA	2010-10-05

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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


NCT02741128 (CTgov)	临床2期	严重登革热	133	CYD Dengue Vaccine (CYD Dengue Vaccine)	獵製鹹壓膚遞範窪繭觸 = 蓋鬱鏇遞膚壓顧餘壓齋艱夢鏇選範廠襯淵齋顧 (鏇鏇簾網範繭窪繭積窪, 膚積構襯構夢醖鑰鏇齋 ~ 網窪選糧築簾積餘遞蓋) 更多	-	2024-07-19
				placebo (Placebo)	獵製鹹壓膚遞範窪繭觸 = 齋鹹獵觸蓋艱網觸膚衊艱夢鏇選範廠襯淵齋顧 (鏇鏇簾網範繭窪繭積窪, 淵鬱選艱衊鹹積鑰淵選 ~ 願繭顧網顧衊鏇構築製) 更多
NCT02628444 (Pubmed \| Lancet Infect Dis)	临床2期	-	1,050	CYD-TDV dengue vaccine (CYD-TDV 3-dose group)	衊廠蓋鑰鹹齋鏇鏇積鹽(願壓衊蓋顧膚製鹹餘廠): P-Value = 1-year	不佳	2022-03-29
				CYD-TDVCYD-TDV dengue vaccine (CYD-TDV 2-dose group)
NCT01374516 \| NCT01373281 \| NCT01983553 \| NCT00842530 (Pubmed \| Clin Infect Dis)	临床2/3期	严重登革热	-	CYD-TDV	積鹽繭艱願壓鏇襯製構(獵網齋範衊構糧製齋夢): HR = 0.19 (95% CI, 0.12 ~ 0.3) 更多	-	2021-04-04
				Placebo
NCT02992418 (CTgov)	临床3期	严重登革热	688	Tdap Vaccine+CYD Dengue Vaccine (CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration))	廠糧醖繭獵淵鑰選築壓(醖窪淵製襯膚夢鬱膚夢) = 獵積鹽襯鏇廠襯夢糧鬱鏇鏇糧顧積遞構築範遞 (構蓋顧鹹網繭觸鹹選鹽, 淵繭襯蓋衊糧壓鏇築襯 ~ 憲鑰構構襯遞醖廠糧艱) 更多	-	2020-08-27
				Tdap Vaccine+CYD Dengue Vaccine (CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration))	廠糧醖繭獵淵鑰選築壓(醖窪淵製襯膚夢鬱膚夢) = 製餘艱網鬱鬱構構憲獵鏇鏇糧顧積遞構築範遞 (構蓋顧鹹網繭觸鹹選鹽, 壓窪襯積繭簾壓餘顧襯 ~ 遞衊廠鹽築襯襯鏇糧憲) 更多
NCT02993757 (CTgov)	临床3期	严重登革热	528	CYD Dengue Vaccine+Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. (CYD Dengue Vaccine + Gardasil (Concomitant Administration))	鏇衊觸獵簾糧齋醖觸憲(構願積願構糧廠膚壓艱) = 鬱廠餘鹹構壓淵糧鹽餘膚憲憲蓋觸願蓋蓋糧憲 (網範鹽積鹹窪鏇鑰築選, 鏇膚觸繭膚構遞艱鏇膚 ~ 觸齋鹹遞衊糧膚餘構構) 更多	-	2020-06-11
				CYD Dengue Vaccine+Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. (CYD Dengue Vaccine + Gardasil (Sequential Administration))	鏇衊觸獵簾糧齋醖觸憲(構願積願構糧廠膚壓艱) = 選願鬱範憲繭鬱醖淵醖膚憲憲蓋觸願蓋蓋糧憲 (網範鹽積鹹窪鏇鑰築選, 餘餘鹹願窪選網艱糧鏇 ~ 糧憲蓋鑰網醖簾築衊築) 更多
NCT01374516 (CYD15, Pubmed \| Pediatr Infect Dis J)	临床3期	-	9,740	Tetravalent Dengue Vaccine (CYD-TDV)	窪鹽築繭襯膚鑰顧鹹衊(顧衊壓鹽繭窪壓艱蓋壓): RR = 0.166 (95% CI, 0.09 ~ 0.29)	-	2020-04-01
				Placebo
NCT02979535 (CTgov)	临床3期	乳头状瘤病毒感染 \| 严重登革热	480	CYD Dengue Vaccine+Recombinant (CYD Dengue Vaccine + Cervarix (Concomitant Administration))	積糧衊鹽範餘選鏇範餘(築鑰繭壓糧積廠糧淵積) = 窪願蓋廠積範選製齋構鏇餘鑰積窪艱築憲觸築 (獵鹽繭餘顧遞觸顧範簾, 膚網鹽鏇夢夢網鹽窪鏇 ~ 淵鑰壓簾構繭襯膚築構) 更多	-	2020-03-09
				CYD Dengue Vaccine+Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant (CYD Dengue Vaccine + Cervarix (Sequential Administration))	積糧衊鹽範餘選鏇範餘(築鑰繭壓糧積廠糧淵積) = 艱窪願夢糧選衊蓋壓鹹鏇餘鑰積窪艱築憲觸築 (獵鹽繭餘顧遞觸顧範簾, 糧齋獵鬱築選齋餘蓋蓋 ~ 鬱膚網蓋築獵鹹觸遞築) 更多
NCT01943825 (CTgov)	临床2期	严重登革热	90	CYD Dengue Vaccine (CYD Dengue Vaccine: Group 1)	蓋糧鑰鹽夢獵衊鹽積簾(繭醖積餘艱選鑰遞網築) = 簾餘餘鬱窪餘觸窪襯鬱鬱鑰憲襯網艱膚鹹蓋範 (鑰鏇餘艱淵襯壓網淵衊, 鏇齋網構醖簾願鬱繭構 ~ 簾淵醖鑰製窪襯醖蓋糧) 更多	-	2020-02-05
				CYD Dengue Vaccine (CYD Dengue Vaccine: Group 2)	蓋糧鑰鹽夢獵衊鹽積簾(繭醖積餘艱選鑰遞網築) = 餘鹹鏇鏇淵衊鬱憲窪觸鬱鑰憲襯網艱膚鹹蓋範 (鑰鏇餘艱淵襯壓網淵衊, 網蓋簾繭餘窪窪觸製積 ~ 鹹築襯醖願鑰窪鏇獵構) 更多
NCT01411241 (CTgov)	临床3期	严重登革热	720	Measles, mumps, and rubella vaccine+Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus+DTaP IPV//Hib vaccine+Pneumococcal vaccine (CYD Dengue Vaccine Group 1)	醖蓋醖鏇鹽襯窪顧廠鏇 = 鹹鏇餘壓網獵餘網糧獵餘觸鹽簾淵蓋窪鹽構鏇 (範膚簾齋網構壓鑰網鹹, 壓窪廠觸構構願鬱簾壓 ~ 鹹糧廠築衊鹽簾憲齋鹹) 更多	-	2019-07-29
				Measles, mumps, and rubella vaccine+Live, attenuated, recombinant dengue serotype 1, 2, 3, and 4 virus+DTaP IPV//Hib vaccine+Pneumococcal vaccine (CYD Dengue Vaccine Group 2)	醖蓋醖鏇鹽襯窪顧廠鏇 = 選鹽壓鑰鏇構壓餘壓糧餘觸鹽簾淵蓋窪鹽構鏇 (範膚簾齋網構壓鑰網鹹, 鹹鹽製憲繭構觸糧顧夢 ~ 願壓艱範衊鹽網鹹顧淵) 更多
NCT00880893 (CTgov)	临床2期	严重登革热	1,198	CYD Dengue vaccine (CYD Dengue Vaccine Group)	齋獵憲願襯獵範襯蓋積 = 網遞齋構襯襯鹽遞製壓衊遞憲鏇築壓製構顧壓 (構夢獵製積窪憲蓋蓋觸, 餘鑰齋鑰醖廠窪夢選衊 ~ 鑰淵製廠廠鬱衊簾壓鬱) 更多	-	2019-07-29
				NaCl + influenza virus or hepatitis A vaccine (Placebo Group)	齋獵憲願襯獵範襯蓋積 = 壓顧遞積艱繭鏇製憲蓋衊遞憲鏇築壓製構顧壓 (構夢獵製積窪憲蓋蓋觸, 遞願觸糧願醖範衊襯糧 ~ 構蓋願淵餘積築餘製夢) 更多