预约演示

更新于：2025-07-15

Vocimagene amiretrorepvec

更新于：2025-07-15

概要

概要

基本信息

药物类型

基因疗法

别名

Flucytosine prodrug activating therapy、Retroviral replicating viral、RRV

+ [10]

靶点

CDA

作用方式

调节剂

作用机制

CDA调节剂(胞嘧啶核苷脱氨酶调节剂)

治疗领域

肿瘤神经系统疾病其他疾病

在研适应症

高级别胶质瘤复发性胶质母细胞瘤胶质母细胞瘤

非在研适应症

膀胱癌结直肠癌多形性胶质母细胞瘤+ [13]

原研机构

在研机构

非在研机构

权益机构

Forte Biosciences, Inc.

杭州索元生物医药股份有限公司

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评快速通道 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、优先药物（PRIME） (欧盟)

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结构/序列

Sequence Code 540803104

关联

项与 Vocimagene amiretrorepvec 相关的临床试验

NCT06504381

/ Recruiting临床1/2期IIT

A Phase I/IIa Study to Evaluate the Efficacy of DB107-RRV (Formerly Toca511), Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination With DB107-FC (Formerly Toca FC) and Radiation Therapy or DB107-FC, Temozolomide (TMZ) and Radiation Therapy in Patients With Newly Diagnosed High Grade Glioma

This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.

开始日期2025-01-08

申办/合作机构

The University of California, San Francisco

[+2]

NCT06264388

/ Recruiting临床2期IIT

A Biomarker-Guided Phase 2 Study of DB107-RRV (Retroviral Replicating Vector) Combined With DB107-Flucytosine Extended-Release Tablets in Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.

开始日期2024-05-01

申办/合作机构

University of Miami

[+2]

NCT04105374

/ Withdrawn临床2/3期IIT

A Phase II/III Randomized, Open-Label Study of Toca 511, A Retroviral Replicating Vector, Combined With Toca FC With Temozolomide and Radiation Followed by Adjuvant Temozolomide and Toca FC Compared to Temozolomide and Radiation Followed by Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

This phase II/III trial studies how well vocimagene amiretrorepvec (Toca 511) and extended release flucytosine (Toca FC) work when added to the usual treatment (temozolomide and radiation therapy) in treating patients with newly diagnosed glioblastoma. Toca 511 is a live virus that has been built to carry a gene into tumor cells. This gene carries instructions that cause the tumor cells to turn Toca FC, typically used to treat fungal infections, into a drug that may kill the tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving Toca 511 and Toca FC in addition to the usual treatment (temozolomide and radiation therapy) may help shrink or stabilize cancer or extend the life of patients with newly diagnosed glioblastoma.

开始日期2020-01-31

申办/合作机构

NRG Oncology

[+1]

100 项与 Vocimagene amiretrorepvec 相关的临床结果

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100 项与 Vocimagene amiretrorepvec 相关的转化医学

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100 项与 Vocimagene amiretrorepvec 相关的专利（医药）

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267

项与 Vocimagene amiretrorepvec 相关的文献（医药）

2025-02-25·JOURNAL OF VIROLOGY

Generation of chimeric forms of rhesus macaque rhadinovirus expressing KSHV envelope glycoproteins gH and gL for utilization in an NHP model of infection

Article

作者: Wong, Scott W. ; Li, Helen ; Axthelm, Michael K. ; Govindan, Aparna N. ; McDonald, Kaidlyn A. ; Estep, Ryan D.

ABSTRACT:

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with Kaposi’s sarcoma and B cell malignancies. Like all herpesviruses, KSHV contains conserved envelope glycoproteins (gps) involved in virus binding, entry, assembly, and release from infected cells, which are also targets of the immune response. Due to the lack of a reproducible animal model of KSHV infection, the precise functions of the KSHV gps during infection in vivo are not completely known. Fortunately, a nonhuman primate (NHP) model of KSHV infection and disease has been established utilizing closely related rhesus macaque rhadinovirus (RRV) that naturally infects rhesus macaques (RM) and possesses analogous gps to KSHV. To address the roles conserved envelope gps gH and gL play during KSHV infection in vivo , we utilized the pathogenic RRV 17577 BAC to generate chimeric forms of RRV expressing KSHV gL or KSHV gH/gL, as well as an RRV mutant lacking gL expression. These viruses incorporate KSHV gH and gL into infectious virions, and although they display variable replication and differing plaque phenotypes in primary rhesus fibroblasts, they retain the ability to infect human B cells in vitro . Importantly, we also demonstrate that RRV gp chimeras can infect RM and induce the development of antibodies against KSHV. Overall, this work demonstrates that RRV gp chimeras can serve as important tools to assess the role of KSHV gH/gL in infection and disease while also providing an NHP model for testing the efficacy of KSHV gH and gL neutralizing antibodies and vaccine strategies to prevent and treat KSHV infection.

IMPORTANCE:

Rhesus macaque rhadinovirus (RRV) is a rhesus macaque homolog of KSHV and serves as a model system for examining Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and pathogenesis in vivo . KSHV and RRV both encode conserved herpesvirus envelope glycoproteins, including gH and gL, that are important for regulating entry into host cells. In this study, we utilized the RRV BAC system to generate chimeric forms of RRV expressing KSHV gH and gL, as well as a mutant form of RRV lacking gL expression. Although these mutant and chimeric viruses can replicate in vitro , they do display growth properties different from wild-type RRV. Importantly, we demonstrate that RRV gp chimeras are capable of infecting rhesus macaques in vivo , inducing B cell hyperplasia, and promoting the development of anti-viral antibody responses that can also recognize KSHV antigens. RRV gp chimeras provide a novel system that allows for the examination of the role of KSHV gH and gL during infection in vivo .

2024-12-11·mBio

Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8 ⁺ T cell responses against an arthritogenic alphavirus

Article

作者: Liu, Tian-Tian ; Wagoner, Ngan ; Handley, Scott A. ; Bullock, Christopher B. ; Diamond, Michael S. ; Ohara, Ray A. ; Murphy, Kenneth M. ; Desai, Pritesh ; Wang, Leran ; Peters, Bjoern ; Ware, Brian C. ; Morrison, Thomas E.

ABSTRACT:

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8 + T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8 + T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8 + T cells. After footpad injection, we detected fewer gp33-specific CD8 + T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot. However, less RRV RNA was detected in the DLN compared to LCMV, with RRV localizing principally to the subcapsular region and LCMV to the paracortical T-cell zones. Single-cell RNA-sequencing analysis of adoptively transferred gp33-specific transgenic CD8 + T cells showed rapid differentiation into effector cells after LCMV but not RRV infection. This defect in RRV-specific CD8 + T effector cell maturation was corrected by local blockade of type I interferon (IFN) signaling, which also resulted in increased RRV infection in the DLN. Studies in Wdfy4−/− , CD11c-Cre B2mfl/fl , or Xcr1-Cre Ifnar1fl/fl mice that respectively lack cross-presenting capacity, MHC-I antigen presentation by dendritic cells (DCs), or type I IFN signaling in the DC1 subset show that RRV-specific CD8 + T-cell responses can be improved by enhanced direct antigen presentation by DCs. Overall, our experiments suggest that antiviral type I IFN signaling in DCs limits direct alphavirus infection and antigen presentation, which likely delays CD8 + T-cell responses.

IMPORTANCE:

Chronic arthritis and musculoskeletal disease are common outcomes of infections caused by arthritogenic alphaviruses, including Ross River virus (RRV), due to incomplete virus clearance. Unlike other viral infections that are efficiently cleared by cytotoxic CD8 + T cells, RRV infection is surprisingly unaffected by CD8 + T cells as mice lacking or having these cells show similar viral persistence in joint and lymphoid tissues. To elucidate the basis for this deficient response, we measured the RRV-specific CD8 + T-cell population size and activation state relative to another virus known to elicit a strong T-cell response. Our findings reveal that RRV induces fewer CD8 + T cells due to limited infection of immune cells in the draining lymph node. By increasing RRV susceptibility in antigen-presenting cells, we elicited a robust CD8 + T-cell response. These results highlight antigen availability and virus tropism as possible targets for intervention against RRV immune evasion and persistence.

2024-12-05·NEURO-ONCOLOGY

Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma

Article

作者: Collins, Sara A ; Nejo, Takahide ; Kasahara, Noriyuki ; Chuntova, Pavlina ; Patel, Trishna S ; Yamamichi, Akane ; Montoya, Megan ; Okada, Hideho

Abstract:

Background:

Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could “reprogram” intratumoral MDSCs into antigen-presenting cells and thereby restore T-cell responses.

Methods:

Effects of RRV-IRF8 on survival and tumor growth kinetics were examined in the SB28 murine GBM model. The immunophenotype was analyzed by flow cytometry and gene expression assays. We assayed functional immunosuppression and antigen presentation by ex vivo T-cell-myeloid co-culture.

Results:

Intratumoral injection of RRV-IRF8 in mice bearing intracerebral SB28 glioma significantly suppressed tumor growth and prolonged survival. RRV-IRF8 treated tumors exhibited significant enrichment of cDC1s and CD8+ T-cells. Additionally, myeloid cells derived from RRV-IRF8 tumors showed decreased expression of the immunosuppressive markers Arg1 and IDO1 and demonstrated reduced suppression of naïve T-cell proliferation in ex vivo co-culture, compared to controls. Furthermore, DCs from RRV-IRF8 tumors showed increased antigen presentation compared to those from control tumors. In vivo treatment with azidothymidine (AZT), a viral replication inhibitor, showed that IRF8 transduction in both tumor and non-tumor cells is necessary for survival benefit, associated with a reprogrammed, cDC1- and CD8 T-cell-enriched TIME.

Conclusions:

Our results indicate that reprogramming of glioma-infiltrating myeloid cells by in vivo expression of IRF8 may reduce immunosuppression and enhance antigen presentation, achieving improved tumor control.

项与 Vocimagene amiretrorepvec 相关的新闻（医药）

2025-03-29

·CPHI制药在线

科睿药业抗流感1类新药玛舒拉沙韦获批上市；默沙东近20亿美元引进恒瑞Lp(a)抑制剂 | 制药在线一周药闻复盘

点击蓝字关注我们本周，热点较多。首先看审评审批方面，国内外都有两个重磅药获批，国内来说，科睿药业抗流感1类新药玛舒拉沙韦获批上市，国外而言，first-in-class口服抗生素获FDA批准上市，成为近30年来首个获批治疗uUTI的新型口服抗生素。其次看研发方面，多个药物取得重要进展，值得一提的就是，中美瑞康公布小核酸癌症新药积极结果，完全缓解率超66%，但比较遗憾的是，Cassava Sciences阿尔茨海默病新药Ⅲ期研究失败；最后是交易及投融资方面，比较值得关注的就是，默沙东近20亿美元引进恒瑞Lp(a)抑制剂。本期盘点包括审评审批、研发以及交易及投融资三大板块，统计时间为2025.3.24-3.28，包含25条信息。审评审批NMPA上市批准1、3月27日，NMPA官网显示，青峰医药下属子公司科睿药业1类新药玛舒拉沙韦片（GP681片）获批上市，用于既往健康的12岁及以上青少年和成人单纯性甲型和乙型流感患者的治疗，不包括存在流感相关并发症高风险的患者。玛舒拉沙韦片是青峰医药与银杏树药业联合开发的一种聚合酶酸性蛋白（PA）抑制剂，患者全病程只需服药一次。申请2、3月24日，CDE官网显示，Plethora Solutions和复星医药共同申报的5.1类新药利多卡因丙胺卡因气雾剂（研发代号：PSD502）申报上市，用于治疗早泄。这是一款利多卡因及丙胺卡因的专有配方，为一款定量透皮喷雾，最早于2013年11月在欧盟获批上市，2018年12月，复星医药控股子公司万邦生化医药获得该产品在中国商业化权益。3、3月25日，CDE官网显示，施维雅申报的5.1类新药艾伏尼布片新适应症申报上市，推测适应症为联合阿扎胞甘一线治疗携带易感IDH1突变的AML患者。艾伏尼布片是一种针对IDH1突变酶的口服靶向抑制剂，此前已作为“临床急需境外新药”在国内获批，用于治疗携带IDH1易感突变的复发或难治性急性髓系白血病（AML）成人患者。临床批准 4、3月24日，CDE官网显示，恩华药业1类新药NH140068片获批临床，拟开发治疗精神分裂症。NH140068是一款适于口服的多种神经递质受体激动剂，为新一代治疗精神分裂症的创新药。本次是该产品首次在中国获批临床。5、3月25日，CDE官网显示，科伦博泰1类新药SKB107注射液获批临床，拟开发用于晚期实体瘤骨转移。这是该公司与西南医科大学附属医院共同开发的靶向肿瘤骨转移的放射性核素偶联药物（RDC）药物。本次是该产品首次在中国获批IND。6、3月25日，CDE官网显示，映恩生物1类新药注射用DB-2304获批临床，拟开发治疗系统性红斑狼疮。DB-2304是映恩生物自主研发的靶向BDCA2这一浆细胞样树突状细胞（pDC）特异靶点的ADC产品，具有潜在“first-in-class”。7、3月25日，CDE官网显示，复宏汉霖的HLX79注射液获批Ⅱ期临床，联合利妥昔单抗（汉利康）治疗活动期肾小球肾炎。HLX79是复宏汉霖许可引进的一款潜在“first-in-class”人唾液酸酶融合蛋白，2024年12月，复宏汉霖与Palleon达成一项9530万美元的授权合作，获得HLX79在中国的独家许可。8、3月27日，CDE官网显示，华东医药1类新药HDM3019获批临床，拟开发治疗类风湿关节炎。HDM3019是靶向OX40L和TNFα的双特异性抗体。华东医药于2024年8月与IMBiologics达成独家许可协议，获得两款自身免疫性疾病新药在中国等37个亚洲国家的权益，其中就包括了这款IMB-101。该项合作的总金额超3亿美元。9、3月27日，CDE官网显示，阿斯利康旗下Alexion的1类新药Eneboparatide注射液获批临床，拟开发治疗慢性甲状旁腺功能减退症。这是一款治疗性多肽，2024年3月，阿斯利康宣布以10.5亿美元收购罕见内分泌疾病领域生物技术公司Amolyt Pharma，从而获得这款名为eneboparatide（AZP-3601）的Ⅲ期临床阶段研发项目。10、3月27日，CDE官网显示，礼来申报的1类新药注射用LY4052031获批临床，拟单药用于治疗晚期或转移性尿路上皮癌或其他实体瘤。这是一款在研的抗Nectin-4抗体偶联药物（ADC），正在国际范围内开展Ⅰ期临床研究。本次是该产品首次在中国获批IND。优先审评11、3月28日，CDE官网显示，默沙东的Clesrovimab注射液拟纳入优先审评，用于即将进入或出生在第一个呼吸道合胞病毒（RSV）流行季的新生儿和婴儿预防RSV所致的下呼吸道感染。Clesrovimab是一种在研的半衰期延长的单抗，可作为被动免疫手段，用于预防RSV疾病。2024年12月，该产品向FDA批准上市，用于保护婴儿在其首个RSV季节免受RSV疾病的侵害。FDA预定在2025年6月前完成审评。突破性疗法12、3月27日，CDE官网显示，恒瑞医药1类新药HRS-5965胶囊拟纳入突破性治疗品种，适应症为原发性IgA肾病。HRS-5965为一款补体因子B抑制剂。该产品针对原发性IgA肾病适应症目前正处于Ⅱ期临床阶段。HRS-5965的首个Ⅲ期临床正在进行中，旨在评估HRS-5965胶囊对比一款C5补体抑制剂治疗阵发性睡眠性血红蛋白尿（PNH）的有效性与安全性。FDA上市批准13、3月26日，FDA官网显示，GSK的Gepotidacin（商品名：Blujepa）获批上市，用于治疗单纯性尿路感染（uUTI）的成人及12岁以上青少年患者。Gepotidacin是一款具有独特作用机制的口服“first-in-class”抗生素。14、3月26日，FDA官网显示，Exelixis的卡博替尼新适应症获批，用于治疗既往接受过治疗、不可切除的、局部晚期或转移性的、分化良好的胰腺神经内分泌肿瘤（pNET）和胰腺外NET（epNET）儿童（≥12岁）和成人患者。这是第一个获FDA批准用于系统治疗无论原发肿瘤部位、分级、生长抑素受体表达和功能状态的经治NET的药物，于2012年11月在美国获批上市。临床批准15、3月24日，FDA官网显示，神济昌华的SNUG01获批Ⅰ/Ⅱa期国际多中心注册临床试验，用于治疗肌萎缩侧索硬化（ALS）。SNUG01是以重组腺相关病毒9型（rAAV9）为载体，通过鞘内注射（IT）的方式，将人源TRIM72基因靶向递送至神经元。16、3月24日，FDA官网显示，云顶新耀的EVM14注射液获批临床。EVM14是一款靶向多种肿瘤相关抗原（TAA）的通用型的现货肿瘤治疗性疫苗，拟用于非小细胞肺癌、头颈癌等多种癌症的治疗。该产品通过将编码多种肿瘤相关抗原的mRNA原液包封在脂质系统中配制而成。优先审评17、3月25日，FDA官网显示，赛诺菲的Tolebrutinib获优先审评，用于治疗非复发性继发进展型多发性硬化症（nrSPMS）并延缓成人患者独立于复发活动的残疾进展，PDUFA日期为2025年9月28日。欧盟也正在审评该药的上市申请。如果获得批准，Tolebrutinib将成为第一种也是唯一一款既能治疗nrSPMS又能减缓残疾累积而不受复发活动影响的脑穿透性BTK抑制剂。研发临床状态18、3月24日，索元生物宣布，其DB107治疗新诊断的高级别胶质瘤的临床Ⅰ/Ⅱ期试验首例受试者完成入组。这是一项评估DB107在切除时和术后静脉注射，联合DB107FC和放射治疗或DB107FC、替莫唑胺(TMZ)和放射治疗对新诊断的高级别胶质瘤患者进行治疗的研究，计划招募70名患者，证明DB107在生物标志物阳性脑瘤患者中无进展生存率的改善。临床数据19、3月24日，Opthea Limited公布了Sozinibercept治疗湿性年龄相关性黄斑变性（wAMD）的Ⅲ期COAST研究。结果显示，该研究未达到主要终点。在总体人群中，Sozinibercept（每4周1次）联合阿柏西普组、Sozinibercept（每8周1次）联合阿柏西普组和安慰剂联合阿柏西普组的BCVA评分分别增加了13.5个字母、12.8个字母和13.7个字母，组间p值分别为0.86和0.42。Sozinibercept是一款靶向血管内皮生长因子受体3（VEGFR3）的Fc融合蛋白，可阻断VEGF-C、VEGF-D与VEGFR2、VEGFR3的结合。20、3月24日，中美瑞康公布了RAG-01治疗非肌层浸润性膀胱癌（NMIBC）Ⅰ期临床试验的积极初步数据。数据显示，在接受卡介苗（BCG）治疗失败的患者中，最低两个剂量组的原位癌（CIS）患者完全缓解率（CR）达到66.7%，且安全性表现优异。RAG-01是一种创新性的saRNA（小激活RNA）疗法，旨在上调p21肿瘤抑制基因的表达。21、3月25日，Cassava Sciences公布了Simufilam治疗轻度至中度阿尔茨海默病（AD）的Ⅲ期REFOCUS-ALZ研究数据。数据显示，未达到主要终点。此前，该研究因Ⅲ期RETHINK-ALZ研究失败在2024年11月25日终止开展。Simufilam是一款靶向错构的细丝蛋白A（FLNA）的口服小分子药物。22、3月28日，劲方医药公布了氟泽雷塞联合西妥昔单抗一线治疗NSCLC的最新Ⅱ期（KROCUS）数据。数据显示，该药具有优秀的总体疗效、显著的脑转移患者肿瘤缓解、以及优于二线及以上氟泽雷塞单药疗法的安全性/耐受性；相较于包含免疫疗法的当前一线NSCLC标准治疗，KROCUS方案也提示了针对KRAS突变患者的更优治疗潜力。氟泽雷塞为一款KRAS G12C抑制剂，由信达生物和劲方医药合作开发，是中国批准上市的首个KRAS抑制剂药物。交易及投融资23、3月24日，联邦制药宣布，其全资附属公司联邦生物已与诺和诺德签订协议。诺和诺德将获得UBT251全球（不包括中国大陆、中国香港、中国澳门和中国台湾地区）的开发、生产和商业化权益。联邦生物保留中国权益。UBT251是一款长效GLP-1R/GIPR/GCGR三重激动剂，拟开发用于治疗肥胖症、2型糖尿病和其他疾病。根据协议，联邦生物将获得2亿美元首付款和最高18亿美元的潜在里程碑付款，以及分层销售提成。24、3月25日，恒瑞医药宣布，与默沙东就其脂蛋白(a)[Lp(a)]口服小分子项目（包括名为HRS-5346先导化合物）达成独家许可协议。根据协议，恒瑞医药将HRS-5346在大中华区以外的全球范围内开发、生产和商业化的独家权利有偿许可给默沙东。恒瑞医药将收取2亿美元的首付款，并有资格获得不超过17.7亿美元的与特定的开发、监管和商业化相关的里程碑付款，以及如果相关产品获批上市，基于HRS-5346的净销售额的销售提成。25、3月26日，浦合医药宣布，与拜耳就BAY 3713372（浦合原代号PH020）达成全球许可协议。根据协议，拜耳获得开发、制造和商业化该产品的全球独家许可。BAY 3713372是一种口服的强效选择性MTA协同PRMT5抑制剂，拜耳已招募首例患者参与Ⅰ期人体首次剂量爬坡临床试验，研究该产品用于治疗MTAP缺失型实体瘤。END2025金笔奖征文活动开启，来投稿吧！领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床3期上市批准临床申请优先审批申请上市

2025-03-26

·医药观澜

索元生物在研脑瘤基因疗法临床首位受试者完成入组

▎药明康德内容团队报道 3月24日，索元生物宣布其创新药DB107治疗新诊断的高级别胶质瘤的临床1/2期试验首例受试者完成入组。这项名为“评估DB107 RRV疗效的1/2a期研究，在切除时和术后静脉注射，联合DB107FC和放射治疗或DB107FC、替莫唑胺 (TMZ) 和放射治疗对新诊断的高级别胶质瘤患者进行治疗”的临床试验是由三家著名脑瘤研究机构，加州大学旧金山医学院、南加州大学及加州大学圣地亚哥医学院共同发起。该试验计划招募70名患者，其目标是证明DB107在生物标志物阳性脑瘤患者中无进展生存率的改善。 DB107为一种组合疗法，即由前药激活剂基因疗法的逆转录病毒复制载体（RRV） DB107-RRV（vocimagene amiretrorepvec）和口服前药DB107-FC（缓释5-氟胞嘧啶）两部分组成。DB107-RRV是一种肿瘤内和静脉注射的逆转录病毒复制载体（RRV），可将口服的5FC在肿瘤部位转化为强效化疗药5-氟尿嘧啶（5-FU）。这一疗法可使瘤内浓度达到5-FU全身用药的30-50倍，在杀死局部细胞的同时，最大限度地减少了全身暴露和5-FU的脱靶毒性。通过过往临床试验的回顾性研究，索元生物利用其独特的DGM生物标志物发现平台，发现了一个全新的生物标志物Denovo Genomic Marker 7（DGM7）。DGM7阳性的患者的总体生存率显著优于DGM7阴性患者，同时也显著优于采用标准治疗的患者。加州大学旧金山医学院神经肿瘤学家兼首席研究员Nicholas Butowski博士说：“招募第一批患者是推进高级胶质瘤患者治疗选择的重要里程碑。我们认为这项试验将为患者及提高新诊断患者的生存率提供有高度的价值。” 该项目合作单位Anova CEO Chris Beardmore博士说：“这是一项革命性的科学研究，治疗方法藉由基因疗法感染癌症细胞进行化疗。因此可以显著降低化疗治疗常见的全身毒性并且进一步感染无法通过手术和其他干预措施去除的癌细胞，大幅改善脑瘤患者的病症。” 索元生物创始人暨董事长罗文博士表示：“高级别胶质瘤（High-grade gliomas, HGG）仍然是治疗最具挑战性的癌症之一，其治疗选择有限且病情高度复杂。该疾病的治疗方法在过去20年中几乎没有变化。DGM7则是DGM发现平台首次在基因治疗药物中发现的全新生物标志物，是索元生物DGM平台在小分子药物之外的成功案例，再次证明了DGM平台的可持续性和可扩展性。这个项目将精准医疗、基因治疗及化药有机的结合起来，这种组合疗法旨在根除肿瘤细胞，同时以最小的毒性刺激强大而持久的抗癌免疫反应。” 参考资料： [1]索元生物新闻稿. 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

基因疗法放射疗法

2025-03-07

·PipelineReview

Anova Announces First Patient Enrolled to Phase 1/2a Study of DB107 for the Treatment of High-Grade Gliomas

LONDON, UK & CHICAGO, IL, USA I March 05, 2025 I Anova Enterprises, Inc. (Anova), a technology-enabled CRO dedicated to accelerating promising treatments, has announced enrollment of the first two patients in the highly anticipated study of DB107 for the treatment of brain tumors. The Phase 1/2a clinical trial is a multicenter, open-label study designed to confirm whether treatment DB107, when added to standard-of-care (SOC), provides clinical benefit to patients with newly diagnosed high-grade gliomas (HGG) when compared to historical performance. The study is funded with a California Institute for Regenerative Medicine (CIRM) grant to advance the development of DB107 in patients with newly diagnosed high-grade glioma. Led by Noriyuki Kasahara, MD, PhD, Principal Investigator, Brain Tumor Research Center (BTRC) at University of California, San Francisco (UCSF), the study is also enrolling at the University of Southern California (USC) and the University of California at San Diego UCSD, and will enroll 70 participants over the coming months. “Enrolling our first patients is an important milestone in our mission to advance treatment options for patients with high- grade glioma,” said Nicholas Butowski, MD, Neuro-Oncologist and Lead Investigator at UCSF. “We are optimistic this trial will provide valuable insights into how we can better treat patients and improve survival in newly diagnosed patients.” High- grade gliomas remain one of the most challenging cancers to treat, with limited treatment options and a high degree of complexity. Treatment for the disease has not changed in 20 years. DB107 is an investigational gene therapy being developed by Denovo Biopharma for the treatment of HGG, including glioblastoma multiforme (GBM). It comprises two components: DB107-RRV (vocimagene amiretrorepvec), a retroviral replicating vector designed to selectively infect and change cancer cells, and DB107-FC, an extended-release oral formulation of 5-fluorocytosine (5-FC), which is converted into a chemotherapeutic agent within the tumor. This combination aims to eradicate tumor cells while stimulating a robust and durable anti-cancer immune response with minimal toxicity. Chris Beardmore said, “This is revolutionary science where the treatment infects cancer cells and genetically changes them to make chemotherapy inside of the infected cells. This is known to reduce systemic toxicity commonly seen with systemic treatments. It also has a chance to infect cells that cannot be removed by surgery and other interventions to improve outcomes in newly diagnosed brain tumor patients.” The clinical trial is currently recruiting eligible patients who meet the study criteria at UCSF, USC and UCSD. Individuals interested in participating or learning more about the trial can contact the study team at info.us@anovaevidence.com . To find out more, contact info.us@anovaevidence.com . About Denovo’s RRV Platform and DB107 DB107 is an innovative approach utilizing a proprietary gene therapy platform, recombinant retroviral vector (RRV) bearing cytosine deaminase, combined with a prodrug of 5-FU (5-FC), to selectively infect and kill cancer cells while stimulating a robust and durable anti-cancer immune response against a tumor with minimal toxicity. DB107 has been tested clinically in solid tumors including recurrent high-grade GBM and colorectal cancer, most recently in a randomized 403-patient Phase 3 trial. DB107 received Orphan Drug Designation in GBM from the FDA and EMA, and Fast Track Designation from the FDA. About Anova Anova Enterprises, Inc. (Anova) is technology enabled concierge research organization committed to accelerating clinical development for start-up biopharmaceutical companies utilizing the company’s proprietary technology platform (AnovaOS™). For more information, please visit www.anovaevidence.com . About Denovo Biopharma Denovo Biopharma LLC (Denovo) is a clinical‑stage biopharmaceutical company that uses a novel biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI) to find new genetic biomarkers predictive of drug efficacy, and then uses these biomarkers to execute efficient clinical trials in targeted patient populations to increase the probability of success. Denovo has eight late‑stage drugs in its pipeline addressing major unmet medical needs in oncology and central nervous system diseases; most of the pipeline are first‑in‑class drugs with global rights. Denovo recently announced a major breakthrough in treatment‑resistant depression (TRD) with its DGM4™ biomarker‑guided DB104 drug (liafensine, a potential first‑in‑class triple reuptake inhibitor for TRD). The global Phase 2b clinical trial of DB104 in DGM4‑positive patients with TRD demonstrated strikingly positive results, with highly significant improvements in symptoms of depression seen in DGM4‑positive patients. Visit www.denovobiopharma.com for additional information. About the California Institute for Regenerative Medicine (CIRM) The California Institute for Regenerative Medicine (CIRM) is a funding agency established by Californians to accelerate regenerative medicine research to deliver treatments for patients with unmet medical needs. Established in 2004 through the passage of Proposition 71, CIRM was initially funded with $3 billion from the state of California to support ongoing research, and in 2020, was funded again with another $5.5 billion through Proposition 14 to continue the Agency’s important work. CIRM has provided billions in funding to support stem cell, genetic research, and development programs in its portfolio. Through the Agency’s research, infrastructure, and education programs, CIRM aims to transform the field of regenerative medicine, stimulate economic growth, and improve the lives of diverse communities throughout the state. For more information go to cirm.ca.gov . SOURCE: Anova Enterprises

临床结果临床2期孤儿药快速通道临床3期

100 项与 Vocimagene amiretrorepvec 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10328	-	-	DB15331

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
多形性胶质母细胞瘤	临床3期	美国	Tocagen, Inc.	2015-11-30
多形性胶质母细胞瘤	临床3期	加拿大	Tocagen, Inc.	2015-11-30
多形性胶质母细胞瘤	临床3期	以色列	Tocagen, Inc.	2015-11-30
复发性胶质母细胞瘤	临床3期	美国	Tocagen, Inc.	2015-11-30
复发性胶质母细胞瘤	临床3期	加拿大	Tocagen, Inc.	2015-11-30
复发性胶质母细胞瘤	临床3期	以色列	Tocagen, Inc.	2015-11-30
复发性恶性胶质瘤	临床3期	美国	Tocagen, Inc.	2015-11-30
复发性恶性胶质瘤	临床3期	加拿大	Tocagen, Inc.	2015-11-30
复发性恶性胶质瘤	临床3期	以色列	Tocagen, Inc.	2015-11-30
高级别胶质瘤	临床2期	美国	Denovo Biopharma LLC	2024-05-01

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临床结果

适应症

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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


ASGCT2023	N/A	肺癌	-	Toca 511Toca 511 (vocimagene amiretrorepvec)5-FCimagene amiretrorepvec) (Toca 511/5-FC treatment)	廠獵艱鬱襯艱夢齋窪壓(蓋餘觸艱獵憲積遞簾選) = 簾蓋夢壓構艱壓遞築窪窪選餘廠艱鑰獵積憲簾 (鏇觸窪繭艱積壓夢鑰網 ) 更多	-	2023-05-01
				Toca 511 (vocimagene amiretrorepvec) (Control group)	廠獵艱鬱襯艱夢齋窪壓(蓋餘觸艱獵憲積遞簾選) = 壓獵餘鏇衊壓憲壓鑰淵窪選餘廠艱鑰獵積憲簾 (鏇觸窪繭艱積壓夢鑰網 ) 更多
NCT02414165 (TOCA 5, Pubmed \| JAMA Oncol)	临床2/3期	复发性恶性胶质瘤	403	Toca 511/FC	鹽選窪廠獵憲鹽淵鏇襯(選築鹽夢廠簾積衊廠憲) = 鹽願蓋淵夢壓鬱築淵膚衊積網襯鬱糧願鬱齋齋 (淵艱膚膚窪鬱製遞壓膚 )	不佳	2020-12-01
				Vocimagene Amiretrorepvec (Standard of Care (SOC))	鹽選窪廠獵憲鹽淵鏇襯(選築鹽夢廠簾積衊廠憲) = 製憲顧蓋蓋膚艱膚衊壓衊積網襯鬱糧願鬱齋齋 (淵艱膚膚窪鬱製遞壓膚 )
NCT02576665 (Toca 6, ASCO_GI2020)	临床1期	结直肠癌	17	Toca 511 & Toca FC	夢廠壓夢製餘觸範糧淵(鬱憲願憲餘觸範夢築繭) = 夢餘鹽願簾鏇遞鬱網壓蓋選築繭觸鏇觸簾繭構 (衊鹹觸鏇廠餘鹹憲醖窪 )	积极	2020-02-04
NCT02576665 (Toca 6, SITC2019)	临床1期	实体瘤	21	Toca 511	膚製獵淵願襯鹽憲願夢(廠醖醖鏇繭網膚觸蓋網) = no related Grade 4 adverse events 遞觸願獵膚襯淵構願獵 (膚蓋糧顧鹹觸築構願糧 )	积极	2019-11-01
NCT02414165 (Toca5, Biospace) 人工标引	临床3期	脑癌	-	Fluorouracil+Vocimagene amiretrorepvec	選鬱範繭範鏇艱簾製築(繭艱憲鬱遞壓繭淵構選) = 網壓願積獵繭艱餘淵繭襯構鹽糧願簾壓膚遞壓 (淵艱製醖鏇獵鹽齋網窪 )	不佳	2019-09-12
				Standard of Care	選鬱範繭範鏇艱簾製築(繭艱憲鬱遞壓繭淵構選) = 遞繭繭齋窪淵遞觸築遞襯構鹽糧願簾壓膚遞壓 (淵艱製醖鏇獵鹽齋網窪 )
ASGCT2019	N/A	食管癌	-	Toca 511	廠膚齋鹹窪顧簾糧鬱構(蓋範鹽鏇積衊範艱鏇獵) = tumor growth in Toca 511/5-FC treated group was significantly inhibited compared to control group 築鏇襯艱蓋廠憲衊積鑰 (範廠網蓋網窪範繭繭遞 ) 更多	-	2019-04-22
				Toca FC
NCT01470794 (Pubmed \| Neuro Oncol) 人工标引	临床1期	复发性恶性胶质瘤	56	5-fluorocytosine+Vocimagene amiretrorepvec (IDH1 mutant and wild-type tumors)	憲構夢壓糧觸觸簾觸選(餘鑰觸廠憲鑰鏇齋艱遞) = 衊鑰遞膚壓夢構淵顧糧衊繭襯願顧鬱繭選願構 (築憲壓艱壓壓齋鹹窪鏇 ) 更多	积极	2018-09-03
NCT01985256 (ATIM-02, SNO2016)	临床1期	复发性恶性胶质瘤	17	Toca 511	壓鹽膚遞構夢糧積築廠(網壓鏇鏇觸壓餘淵鏇餘) = n=2, 18.2% 鹹網襯網選艱鬱製鏇夢 (窪齋夢築醖鹽繭衊顧鬱 ) 更多	积极	2016-11-07
ASTRO2016	N/A	-	-	Toca 511	壓網願鑰醖繭製觸範壓(構廠蓋鹹簾觸鬱齋遞鑰) = 鏇衊簾鏇鏇積鑰齋構網襯鬱鬱願願鹹願壓衊壓 (願夢壓鹽網願範構遞觸 ) 更多	-	2016-10-01
				Toca FC	壓網願鑰醖繭製觸範壓(構廠蓋鹹簾觸鬱齋遞鑰) = 積鬱糧願選構鏇膚壓構襯鬱鬱願願鹹願壓衊壓 (願夢壓鹽網願範構遞觸 ) 更多
NCT02414165 (Pubmed \| Sci Transl Med) 人工标引	临床1期	复发性恶性胶质瘤	45	5-fluorocytosine+vocimagene amiretrorepvec	糧鑰構壓製鹹壓夢糧夢(窪顧艱壓艱鹽鹹蓋製糧) = 繭蓋願顧鹹構觸鑰蓋繭鹹願顧鹹獵繭遞繭簾選 (範鑰鹹鹹壓顧鹽鏇襯蓋, 10.8 ~ 20.0)	积极	2016-06-01
				5-fluorocytosine+subgroup from an external control	-