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2024-09-01

申办/合作机构

The University of California, San Francisco

[+1]

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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项与 Vocimagene amiretrorepvec 相关的文献（医药）

2024-08-01·AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Specific binding sites on Rhesus rotavirus capsid protein dictate the method of endocytosis inducing the murine model of biliary atresia

Article

作者: Singh, Akaljot ; Oyama, Kei ; Jegga, Anil G. ; Meller, Jaroslaw ; Mohanty, Sujit K. ; Temple, Haley ; Hartman, Stephen ; Spearman, Paul ; Donnelly, Bryan ; Mourya, Reena ; Tiao, Greg ; Poling, Holly M. ; McNeal, Monica ; Bondoc, Alexander ; Mowery, Sarah ; Pasula, Rajamouli

In this study, we have determined that the presence of the “SRL” peptide on RRV alters its method of endocytosis and intracellular trafficking through viral binding to heat shock cognate 70 protein. This initiates an inflammatory pathway that stimulates the release of cytokines associated with biliary damage and obstruction.

2024-07-19·JOURNAL OF MEDICAL MICROBIOLOGY

Synoviocytes assist in modulating the effect of Ross River virus infection in micromass-cultured primary human chondrocytes

Article

作者: Lim, Elisa X Y ; Freppel, Wesley ; Rudd, Penny A ; Herrero, Lara J

Graphical abstract:

A schematic representation of the study methodology. Human micromass-cultured chondrocytes were either directly infected with RRV or secondarily through co-culture with RRV-infected FLS. Micromass chondrocytes were analysed after 1, 3 and 5 days post-infection for gene expression using a PCR array and for viral load using genome copy number qPCR. FLS were analysed for viral load via qPCR, and supernatants were analysed for infectious viral particles using a plaque assay.

2024-07-01·Lancet Regional Health-Western Pacific

Current and future burden of Ross River virus infection attributable to increasing temperature in Australia: a population-based study

Article

作者: Capon, Tony ; Anikeeva, Olga ; Damtew, Yohannes Tefera ; Tong, Michael ; Bi, Peng ; Gourley, Michelle ; Morgan, Geoffrey ; Prescott, Vanessa ; Dear, Keith ; Driscoll, Tim ; Zhang, Ying ; Hansen, Alana ; Varghese, Blesson Mathew

Background:

Ross River virus (RRV), Australia's most notifiable vector-borne disease transmitted through mosquito bites, has seen increased transmission due to rising temperatures. Quantifying the burden of RRV infection attributable to increasing temperatures (both current and future) is pivotal to inform prevention strategies in the context of climate change.

Methods:

As RRV-related deaths are rare in Australia, we utilised years lived with disability (YLDs) associated with RRV infection data from the Australian Institute of Health and Welfare (AIHW) Burden of Disease database between 2003 and 2018. We obtained relative risks per 1 °C temperature increase in RRV infection from a previous meta-analysis. Exposure distributions for each Köppen-Geiger climate zone were calculated separately and compared with the theoretical-minimum-risk exposure distribution to calculate RRV burden attributable to increasing temperatures during the baseline period (2003-2018), and projected future burdens for the 2030s and 2050s under two greenhouse gas emission scenarios (Representative Concentration Pathways, RCP 4.5 and RCP 8.5), two adaptation scenarios, and different population growth series.

Findings:

During the baseline period (2003-2018), increasing mean temperatures contributed to 35.8 (±0.5) YLDs (19.1%) of the observed RRV burden in Australia. The mean temperature attributable RRV burden varied across climate zones and jurisdictions. Under both RCP scenarios, the projected RRV burden is estimated to increase in the future despite adaptation scenarios. By the 2050s, without adaptation, the RRV burden could reach 45.8 YLDs under RCP4.5 and 51.1 YLDs under RCP8.5. Implementing a 10% adaptation strategy could reduce RRV burden to 41.8 and 46.4 YLDs, respectively.

Interpretation:

These findings provide scientific evidence for informing policy decisions and guiding resource allocation for mitigating the future RRV burden. The current findings underscore the need to develop location-specific adaptation strategies for climate-sensitive disease control and prevention.

Funding:

Australian Research Council Discovery Program.

项与 Vocimagene amiretrorepvec 相关的新闻（医药）

2024-05-11

·药明康德

一次治疗让失聪儿听力恢复正常的基因疗法；基因编辑新锐获阿斯利康青睐追加投资…… | CGT周报

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。再生元（Regeneron Pharmaceuticals）用于治疗遗传性耳聋的在研基因疗法DB-OTO使1名11个月大患者的听力在接受治疗24周内恢复到了正常水平。阿斯利康（AstraZeneca）完成了对在基因编辑领域深耕多年的Cellectis公司约1.4亿美元的追加股权投资。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF———✦研发进展✦———◇ 再生元公布了其用于治疗遗传性耳聋的在研基因疗法DB-OTO的1/2期临床试验的初步积极结果。一名患者在11个月大时就接受了DB-OTO治疗，在24周内听力恢复到正常水平，而另一名在4岁时接受该疗法的患者也在治疗后6周时初步观察到听力有所改善。这两名儿童都因OTOF基因变异而在出生时患有严重的遗传性耳聋，其中接受治疗的11个月大儿童是全球最早接受基因疗法治疗遗传性耳聋的患者之一。DB-OTO是一种在研细胞选择性腺相关病毒（AAV）基因疗法，旨在通过AAV载体将OTOF基因的健康拷贝传递至耳蜗毛细胞，为因OTOF基因突变导致的先天性深度听力损失患者提供持久的生理性听力。此前，DB-OTO已获得了FDA的孤儿药资格、罕见儿科疾病认定以及快速通道资格。◇ Freeline Therapeutics公司公布了其在研基因疗法FLT201进行中的1/2期GALILEO-1试验的最新临床数据。此次公布的结果显示，FLT201能显著降低此前曾长期使用获批疗法且葡萄糖基神经酰胺（lyso-Gb1）水平持续较高的1型戈谢病患者的lyso-Gb1水平，该指标是临床应答的最佳预测指标之一。此外，患者的骨髓负担和疲劳方面也出现了初步的改善迹象。安全性方面，FLT201具有良好的安全性和耐受性，未出现输注反应或严重不良事件。一些患者的谷丙转氨酶（ALT）水平轻微升高，但通过免疫疗法进行控制后，对疗效没有影响。FLT201是一种潜在“first-in-class”与“best-in-class”的在研AAV基因疗法，用于治疗1型戈谢病成年患者。该疗法旨在提供一次性治疗，以持续增加患者体内GCase表达并减少有害底物的积累，阻止疾病进展，让患者不必终生接受治疗。FLT201采用Freeline的AAVS3衣壳，将新型基因引入肝细胞，生产经过理性设计的GCase变体。在临床前研究中，该GCase变体在溶酶体pH条件下的半衰期比野生型人类GCase增加了20倍以上。在临床前研究中，FLT201可导致GCase高度表达并减少关键组织中的底物。图片来源：123RF◇ Atsena Therapeutics公司公布了其在研基因疗法ATSN-201用于治疗X连锁视网膜劈裂症（XLRS）的1/2期临床试验的新数据。此次公布的数据显示，首个队列（低剂量组）的3名患者中有两名在给药8周后开始出现视网膜分裂的广泛改善。第24周（目前可获得的最新时间点）时，分裂仍在继续改善。在视网膜下注射点内外都发现了分裂腔的改善区域，这表明AAV.SPR正在从注射点横向扩散，与这种新型横向扩散衣壳的预期特征一致。在视网膜结构改善的相同位置也观察到了功能改善。一名患者的视力改善高达14 dB，其中38个位置的视力改善超过7 dB。美国FDA认为，在≥5个预先指定的位置至少改善7 dB是具有临床意义的。该组所有3名XLRS患者对ATSN-201的耐受性良好，未报告严重不良事件。ATSN-201使用的新型扩散衣壳AAV.SPR能够横向扩散到视网膜下注射点以外的位置，实现对中央视网膜的安全和有效的基因递送（在XLRS患者的视网膜中，分裂腔主要集中在中央视网膜部位）。此前的研究显示，AAV.SPR在临床剂量下能够有效递送载荷至视网膜中央凹上的视锥细胞，无需手术分离，并且不会引起炎症。◇ Coave Therapeutics公司新成立的子公司eyeDNA Therapeutics宣布，其用于评估HORA-PDE6b的1/2期临床试验24个月时的随访结果良好。此次公布的结果显示，在接受高剂量治疗且症状较轻的患者亚组中，在24个月时报告了在最佳矫正视力（BCVA）和Goldmann视野（GVF）结果方面的积极疗效。未治眼睛的BCVA与基线相比增加了0.09 LogMar，而经治眼睛的视力保持稳定（+0.02 LogMar）。从基线开始，未治眼睛的GVF平均减少了超过300 deg²，而经治眼睛则相对稳定。在24个月的研究期后，患者对高低两种剂量的HORA-PDE6b耐受性都很好。低剂量组患者的长期数据（5年）发现，未治眼睛的BCVA持续下降，而同一组中经治眼睛的BCVA与基线相比保持稳定。此外，用于评估视杆细胞功能的蓝光全视野刺激测试（FFST）持续显示出经治眼睛的光感知阈值有改善的趋势，具有临床意义。HORA-PDE6b是一种以AAV5为载体的基因疗法，用于治疗PDE6b基因双等位基因突变引起的视网膜色素变性。◇ Neurogene公司公布了其用于治疗Rett综合征的基因疗法NGN-401的1/2期试验的初步安全性和耐受性数据。此次公布的结果显示，在接受治疗后约9个月、6个月和3个月的随访中，三名患者对NGN-401的耐受性普遍良好。大多数不良事件是AAV的已知潜在风险，未报道任何转基因过表达毒性的体征或症状。NGN-401是一种在研AAV基因疗法，递送表达全长人甲基胞嘧啶结合蛋白2（MeCP2）的转基因。NGN-401利用Neurogene专有的基因调控技术，提供高度控制和一致的MeCP2表达，从而避免了与常规基因治疗相关的过表达相关毒性。◇ Lineage Cell Therapeutics公司公布了其同种异体视网膜色素上皮（RPE）细胞疗法RG6501（OpRegen）用于治疗年龄相关性黄斑变性（AMD）继发地理萎缩（GA）的1/2a期临床试验24个月时的数据。结果显示，接受OpRegen细胞后至少2年内，患者眼睛的视网膜外层结构和视觉功能获得了持续的改善，OpRegen细胞可以通过抵消宿主RPE细胞功能障碍和损失来为GA区域内剩余的视网膜细胞提供支持。与基线值相比，队列4中的10名患者的BCVA在接受治疗后24个月时平均增加了5.5个字母，其中5名OpRegen覆盖GA病变更广的患者的治疗效果更好，BCVA平均增加了7.4个字母。经光学相干断层扫描（OCT）检查发现，OpRegen覆盖GA病变更广的患者的视网膜外层结构持续得到改善。◇ Acepodia公司公布了其现货型CD20靶向抗体偶联异体γδ2 T细胞疗法ACE1831用于治疗非霍奇金淋巴瘤的1期剂量递增试验的初步数据。ACE1831利用γδ T细胞上高表达的NK细胞激活受体来清除恶性血细胞，在体外和体内模型中都显示出了对癌细胞增强的细胞毒性。此次公布的结果显示，ACE1831单次给药（最低剂量）治疗后，5名患者中有1名出现完全缓解（CR），3名达到了疾病稳定（SD）。在这些患者中，1名CR和2名SD患者曾接受过CD19靶向嵌合抗原受体（CAR）-T细胞疗法。在ACE1831单次给药后的三个月内，观察到了持续的临床缓解。最低剂量的ACE1831耐受性良好，没有出现与ACE1831相关的严重不良事件，包括移植物抗宿主病（GVHD）、神经毒性、高级别细胞因子释放综合征（CRS）或剂量限制性毒性反应。◇ Fate Therapeutics公司宣布，其现货型CD19靶向CAR-T细胞疗法FT819用于治疗系统性红斑狼疮的1期临床试验完成了首例患者的输注。此外，该公司还公布了FT819治疗复发/难治性B细胞恶性肿瘤（BCM）的1期研究数据，及现货型CD19靶向CAR自然杀伤细胞（NK）细胞疗法FT522治疗复发/难治性B细胞淋巴瘤（BCL）的1期研究的初步临床观察结果。结果显示，FT819和FT522均能诱导快速、深度和持续的CD19+ B细胞耗竭。◇ 瑞吉康宣布其AAV基因治疗药物RJK002注射液获中国国家药品监督管理局药品审评中心（CDE）临床试验默示许可，适应症为肌萎缩侧索硬化。根据瑞吉康新闻稿，该公司的RJK系列药物可“溶解”已经聚集的病原蛋白，阻滞异常聚集蛋白的进一步形成，恢复生物体内蛋白质“相分离”平衡，从而恢复神经元细胞功能，实现对神经退行性疾病的治疗。◇ 百暨基因宣布，其靶向C型凝集素受体家族成员CLL-1的在研自体CAR-T细胞疗法BG1805用于治疗复发/难治性急性髓系白血病的1期临床试验完成了对首例患者的治疗。———✦融资、合作、M&A✦———◇ Cellectis公司宣布，在获得法国经济部批准并满足所有其他成交条件后，阿斯利康完成了对Cellectis公司1.4亿美元的追加投资。Cellectis公司专注于利用其基因编辑技术TALEN和其开创性的电穿孔系统PulseAgile开发候选疗法，以利用免疫系统的力量，靶向并消灭癌细胞。2023年11月，阿斯利康与Cellectis公司宣布达成战略合作和投资协议，将共同合作加速多达10项的下一代细胞与基因疗法开发，将主要专注于医疗需求显著未得到满足的领域，包括肿瘤、免疫学和罕见病等领域。图片来源：123RF◇ OverT Bio公司宣布已筹集到1600万美元的种子轮融资，用于扩大发现平台，重点解决细胞疗法的主要障碍，从而为晚期实体瘤提供持久的治疗方法。该公司将细胞工程技术与大数据相结合，以满足实体肿瘤领域的重大未竟医疗需求。OverT公司开发了独特的大规模并行基因筛选、单细胞多组学和合成生物学平台，用于构建下一代细胞疗法。OverT的核心平台通过搜索遗传信息中的每一个基因，以确定赋予免疫细胞新特性的最佳基因修饰。公司还建立了类似的高通量方法，以发现既安全又有效的新受体和靶点。◇ Nanite公司宣布获得了比尔及梅琳达•盖茨基金会（Bill & Melinda Gates Foundation）资助的180万美元，用于设计和优化递送DNA编码疗法的聚合物递送载体，从而在体内持久生产治疗性抗体。Nanite公司专有的SAYER平台将人工智能驱动的聚合物设计与多重体内筛选相结合，旨在开发出能够特异性递送到组织的潜在“best-in-class”聚合物纳米颗粒（PNP）。SAYER平台已被证明具有很高的递送效率和组织特异性，有望克服病毒载体和脂质纳米颗粒（LNP）的局限性。Nanite的研究在发现安全的PNP以治疗艾滋病方面具有重要意义，该公司正致力于加快基因疗法对艾滋病治疗的影响。◇ 索元生物宣布，美国加州再生医学研究所（CIRM）拨款近1200万美元，用于支持进一步开发其生物标志物指导下的脑瘤基因疗法DB107。根据新闻稿，CIRM授予加州大学旧金山医学院（UCSF）的Noriyuki Kasahara博士和加州几所大学的一组研究人员拨款，用于DB107治疗新确诊的高级别胶质瘤，其中包括胶质母细胞瘤（GBM）的临床1/2期试验。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。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] LATEST DB-OTO RESULTS SHOW DRAMATICALLY IMPROVED HEARING TO NORMAL LEVELS IN A CHILD WITH PROFOUND GENETIC DEAFNESS WITHIN 24 WEEKS AND INITIAL HEARING IMPROVEMENTS IN A SECOND CHILD AT 6 WEEKS. Retrieved May 8, 2024 from https://investor.regeneron.com/news-releases/news-release-details/latest-db-oto-results-show-dramatically-improved-hearing-normal[2] Freeline Presents Positive New Data from Phase 1/2 Trial of FLT201, Its Novel Gene Therapy Candidate for Gaucher Disease, in Late-Breaking Oral Presentation at ASGCT 27th Annual Meeting. Retrieved May 9, 2024 from https://freeline.life/freeline-presents-positive-new-data-from-phase-1-2-trial-of-flt201-its-novel-gene-therapy-candidate-for-gaucher-disease-in-late-breaking-oral-presentation-at-asgct-27th-annual-meeting-2/[3] Atsena Therapeutics Announces Positive Clinical Data from the First Cohort of Phase I/II Trial Evaluating ATSN-201 Gene Therapy for the Treatment of X-linked Retinoschisis (XLRS). Retrieved May 10, 2024, from https://pipelinereview.com/atsena-therapeutics-announces-positive-clinical-data-from-the-first-cohort-of-phase-i-ii-trial-evaluating-atsn-201-gene-therapy-for-the-treatment-of-x-linked-retinoschisis-xlrs/[4] EyeDNA Therapeutics Announces Positive 24-month Data Presented at ARVO from Ongoing Phase I/II Trial of HORA-PDE6b Gene Therapy in Patients with Retinitis Pigmentosa Caused by Bi-allelic Mutations in PDE6b. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/07/2876355/0/en/EyeDNA-Therapeutics-Announces-Positive-24-month-Data-Presented-at-ARVO-from-Ongoing-Phase-I-II-Trial-of-HORA-PDE6b-Gene-Therapy-in-Patients-with-Retinitis-Pigmentosa-Caused-by-Bi-a.html[5] Neurogene Presents Favorable Safety Data from Phase 1/2 Trial of NGN-401 Gene Therapy for Rett Syndrome during ASGCT Annual Meeting. Retrieved May 10, 2024, from https://www.businesswire.com/news/home/20240507803994/en[6] OpRegen® (RG6501) Phase 1/2a Clinical Study 24-Month Visual Acuity Results Featured at 2024 Retinal Cell & Gene Therapy Innovation Summit. Retrieved May 10, 2024, from https://www.businesswire.com/news/home/20240506017390/en[7] Acepodia Announces Preliminary Clinical Data From Phase 1 Clinical Trial of ACE1831, First-Ever Anti-CD20 Antibody Conjugated Allogenic Gamma Delta T Cell Therapy for Non-Hodgkin's Lymphoma. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/acepodia-announces-preliminary-clinical-data-from-phase-1-clinical-trial-of-ace1831-first-ever-anti-cd20-antibody-conjugated-allogenic-gamma-delta-t-cell-therapy-for-non-hodgkins-lymphoma-302139302.html[8] Fate Therapeutics Announces First Lupus Patient Treated in Phase 1 Autoimmunity Study of Off-the-shelf FT819 CAR T-cell Program. Retrieved May 10, 2024, from https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-announces-first-lupus-patient-treated-phase-1[9] 瑞吉康靶向蛋白质异常聚集渐冻症AAV基因治疗药物RJK002获临床试验默示许可.Retrieved May 09, 2024, From https://mp.weixin.qq.com/s/kYCvXneP4B-wj9wkPdiB2g[10] Guangzhou Bio-gene Technologies Announces Initiation of Phase I Clinical Trial for BG1805, a CAR-T Targeting CLL-1. Retrieved May 10, 2024, from https://www.globenewswire.com/news-release/2024/05/02/2874092/0/en/Guangzhou-Bio-gene-Technologies-Announces-Initiation-of-Phase-I-Clinical-Trial-for-BG1805-a-CAR-T-Targeting-CLL-1.html[11] NANITE AWARDED $1.8M TO DEVELOP AI-DRIVEN GENE THERAPY FOR HIV. Retrieved May 10, 2024, from https://www.prnewswire.com/news-releases/nanite-awarded-1-8m-to-develop-ai-driven-gene-therapy-for-hiv-302138913.html[12] Cellectis Announces Completion of the Additional Equity Investment by AstraZeneca. Retrieved May 10, 2024, from https://www.cellectis.com/en/press/cellectis-announces-completion-of-the-additional-equity-investment-by-astrazeneca/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。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

基因疗法免疫疗法孤儿药临床研究临床结果

2024-05-09

·医药观澜

针对脑瘤，索元生物基因疗法获近1200万美元资金支持

5月6日，索元生物宣布，美国加州再生医学研究所（CIRM）拨款近1200万美元，用于支持进一步开发其生物标志物指导下的脑瘤基因疗法DB107。根据新闻稿，CIRM授予加州大学旧金山医学院（UCSF）的Noriyuki Kasahara博士和加州几所大学的一组研究人员拨款，用于DB107治疗新诊断的高级别胶质瘤，其中包括胶质母细胞瘤（GBM）的临床1/2期试验。 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，发现了一个全新的胚系生物标志物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。本次获拨款支持的临床试验的标题为“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DB107-FC和放射治疗或DB107-FC、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”。该研究计划招募多达70名患者，试验的目标是证明无进展生存期的改善。 Kasahara博士表示，很高兴能开展这项同时研究几种新方法的创新试验。除了在肿瘤内和静脉注射DB107-RRV以提供更多的载体暴露机会外，这项研究还将把载体与放疗和替莫唑胺（预计5-FU会对替莫唑胺敏感）结合使用，测试患者的DGM7生物标志物并前瞻性地评估生物标志物对疗效的影响。索元生物首席医疗官兼首席开发官Matthew A. Spear博士表示，非常高兴能继续在高级别胶质瘤患者中开展生物标志物指导的DB107基因疗法的临床开发。索元生物最近宣布，在生物标志物指导下的DB104治疗耐药抑郁症（TRD）的关键性临床试验中取得了积极成果。DGM7则是DGM生物标志物发现平台在基因治疗领域的重大突破，也是在小分子药物之外的成功案例。内容来源于网络，如有侵权，请联系删除。

基因疗法放射疗法临床研究

2024-04-30

·PRNewswire

CIRM Awards $11.8 Million Grant for Clinical Trial in High-Grade Glioma Including Glioblastoma Using DB107, a Novel DGM7™ Genetic Biomarker-Guided Gene Therapy

SAN DIEGO, April 30, 2024 /PRNewswire/ -- Denovo Biopharma LLC (Denovo), a pioneer in applying precision medicine to the development of innovative therapies, today announced that the California Institute for Regenerative Medicine (CIRM) has awarded a $11.8M grant for further development of DB107, Denovo's DGM7™ biomarker–guided late–stage gene therapy, for high–grade glioma (HGG) including glioblastoma (GBM), a malignant brain cancer. CIRM has awarded the grant to Dr. Noriyuki Kasahara, MD, PhD, at the University of California San Francisco (UCSF) and a group of investigators at California universities to conduct a Phase 1/2 clinical trial studying DB107 in patients with newly–diagnosed HGG. Continue Reading The trial, titled "A Phase I/IIa Study to Evaluate the Efficacy of DB107–RRV, Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination with DB107–FC and Radiation Therapy or DB107–FC, Temozolomide (TMZ) and Radiation Therapy in Patients with Newly–Diagnosed High–Grade Glioma," plans to enroll up to 70 patients. The trial aims to demonstrate improvements in progression–free survival. We are thrilled to continue the clinical development of our biomarker-guided DB107 gene therapy in HGG including GBM. Post this DB107 consists of two components: DB107–RRV (vocimagene amiretrorepvec) as a prodrug activator gene therapy and DB107–FC (extended-release 5–fluorocytosine [5–FC]) as an oral prodrug. DB107–RRV, a retroviral replicating vector (RRV) administered intratumorally and intravenously, converts the orally administered 5–FC into the potent chemotherapy agent 5–fluorouracil (5–FU) locally at the tumor sites. This enables intratumoral concentrations 30–50 times of those achievable by 5–FU systemic administration, killing tumor cells while minimizing the systemic exposure and off–target toxicities of 5–FU. Using its proprietary biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI), Denovo discovered the novel germline genetic biomarker, Denovo Genomic Marker 7 (DGM7), which is located in the SHROOM3 gene intron. Retrospective analysis of an earlier randomized clinical trial in patients with recurrent HGG suggested improved overall survival in DGM7–positive patients treated with DB107. "We are excited to conduct this novel trial which will be investigating several new approaches for the first time in patients with newly–diagnosed high–grade glioma. In addition to DB107–RRV being administered both intratumorally and intravenously to provide more exposure, this study will also use the RRV in conjunction with radiation therapy and chemotherapy with temozolomide. In addition to the direct therapeutic effect of gene therapy, glioma cells will be sensitized to these standard therapies by 5–FU generated directly within the patient's tumor from DB107–FC. We are also excited to test the DGM7 biomarker to see if we can identify patients who may benefit the most from this unique gene therapy approach," said Dr. Kasahara. DGM7 status will be determined at the time of enrollment to prospectively assess the effect of the biomarker on clinical outcomes. The study will be conducted at UCSF (Dr. Noriyuki Kasahara, MD, PhD, and Dr. Nicholas Butowski, MD), University of Southern California (USC) (Dr. Thomas Chen, MD, PhD), and University of California San Diego (UCSD) (Dr. David Piccioni, MD, PhD), and will be managed by Anova Enterprises, Inc. "We are thrilled to continue the clinical development of our biomarker–guided DB107 gene therapy in patients with HGG including GBM, a major unmet medical need with less than 5% of GBM patients surviving 5 years," said Dr. Matthew A. Spear, MD, Denovo's Chief Medical Officer and Chief Development Officer. "Alongside our recent announcement of positive results in a Phase 2b clinical trial of our DGM4 biomarker–guided DB104 drug (liafensine) in treatment–resistant depression, the CIRM grant provides continued validation of Denovo's approach to discovering new genetic biomarkers and developing biomarker–guided therapies." About HGG and GBM The most common type of high–grade glioma (HGG) is glioblastoma (GBM), which is also the most common type of adult primary brain cancer, with 18,000 newly–diagnosed patients in the US and 13,000 deaths annually. Standard treatments for patients with newly–diagnosed GBM can include surgery followed by radiation and chemotherapy, but treatment options are limited. The 5–year survival rate of patients with GBM is less than 5%. About DB107 and the DGM7™ Biomarker DB107 is an investigational combination product consisting of the DB107–RRV (vocimagene amiretrorepvec) gene therapy and DB107–FC (extended–release 5–fluorocytosine) oral prodrug. DB107–RRV, an innovative proprietary retroviral replicating vector (RRV), is combined with DB107–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 glioma (rHGG) and colorectal cancer, most recently in a randomized 403–patient Phase 2/3 trial in rHGG including glioblastoma (GBM). Using its proprietary biomarker discovery platform, Denovo discovered the novel genetic biomarker, DGM7, which has been shown to be associated with treatment response to DB107 in patients with rHGG including GBM. DB107 has received Fast Track Designation and Breakthrough Therapy Designation from the FDA, as well as Orphan Drug Designations from the FDA and EMA. 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 for additional information. Contact Michael F. Haller, Chief Business Officer Denovo Biopharma LLC [email protected] SOURCE Denovo Biopharma LLC

临床2期孤儿药快速通道临床结果基因疗法

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
胶质母细胞瘤	临床3期	美国	Tocagen, Inc.	2015-11-30
胶质母细胞瘤	临床3期	加拿大	Tocagen, Inc.	2015-11-30
胶质母细胞瘤	临床3期	以色列	Tocagen, Inc.	2015-11-30
胶质母细胞瘤	临床3期	韩国	Tocagen, Inc.	2015-11-30
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
多形性胶质母细胞瘤	临床3期	韩国	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

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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


ASGCT2023	N/A	肺癌	-	Toca 511 (vocimagene amiretrorepvec)	衊壓齋醖憲襯膚鬱製網(窪製網製鏇鬱積鬱鹹鹽) = 壓餘鬱觸鬱廠鑰鹽觸構鏇膚壓醖鹽顧蓋網艱網 (醖醖鬱鏇餘齋憲艱遞遞 ) 更多	-	2023-05-01
				Toca 511 (vocimagene amiretrorepvec)	衊壓齋醖憲襯膚鬱製網(窪製網製鏇鬱積鬱鹹鹽) = 鑰廠顧膚選醖築襯構鏇鏇膚壓醖鹽顧蓋網艱網 (醖醖鬱鏇餘齋憲艱遞遞 ) 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	衊鹹夢顧獵遞壓構艱夢(淵衊糧窪鬱網窪鑰觸築) = 衊壓構糧鬱壓積觸餘鑰鬱憲糧壓膚壓醖蓋醖壓 (鬱構鬱糧艱膚鹽遞選獵 )	不佳	2020-12-01
				Vocimagene Amiretrorepvec (Standard of Care (SOC))	衊鹹夢顧獵遞壓構艱夢(淵衊糧窪鬱網窪鑰觸築) = 醖製廠膚膚淵齋選觸鑰鬱憲糧壓膚壓醖蓋醖壓 (鬱構鬱糧艱膚鹽遞選獵 )
NCT02576665 (Toca 6, ASCO_GI2020)	临床1期	结直肠癌	17	Toca 511 & Toca FC	餘夢襯窪膚構遞鑰製夢(鑰鏇醖淵齋醖齋膚鬱選) = 憲憲窪觸願製壓夢壓餘觸構廠觸鑰繭膚鹹網範 (觸觸醖選廠艱築醖壓衊 )	积极	2020-02-04
NCT02576665 (Toca 6, SITC2019)	临床1期	实体瘤	21	Toca 511	鏇糧簾觸鏇築鹹獵憲築(衊艱願簾襯鹹壓製鬱壓) = no related Grade 4 adverse events 艱鬱構範衊壓壓構鹹窪 (醖壓衊糧願鹽鑰選範齋 )	积极	2019-11-01
NCT02414165 (Toca5, Biospace) 人工标引	临床3期	脑癌	-	Fluorouracil+Vocimagene amiretrorepvec	願鹽襯鹽鑰遞構積構餘(壓餘鑰鏇餘簾願窪鹹窪) = 淵觸製鹹衊遞鏇觸簾憲廠餘繭積憲醖製範顧淵 (築衊膚積鬱顧觸繭願構 )	不佳	2019-09-12
				Standard of Care	願鹽襯鹽鑰遞構積構餘(壓餘鑰鏇餘簾願窪鹹窪) = 衊顧壓齋夢顧鬱夢鏇鑰廠餘繭積憲醖製範顧淵 (築衊膚積鬱顧觸繭願構 )
ASGCT2019	N/A	食管癌	-	Toca 511	糧積糧鏇鹹顧遞膚繭壓(網顧鬱鏇鏇構廠觸餘壓) = tumor growth in Toca 511/5-FC treated group was significantly inhibited compared to control group 遞蓋鑰壓鹹範艱餘醖鹹 (壓觸壓淵築蓋醖蓋獵餘 ) 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)	餘願顧糧鹽鏇構醖網築(選鹹觸範鑰網艱窪顧繭) = 鹽網繭壓網顧襯醖糧淵廠願淵蓋衊鑰範遞衊構 (糧簾構鏇顧鏇淵網觸膚 ) 更多	积极	2018-09-03
NCT01470794 (S23.006, AAN2018)	临床1期	复发性恶性胶质瘤 IDH1 wildtype \| IDH1 mutant	23	Toca 511	鑰齋糧鬱鑰憲遞築憲夢(鬱遞鬱醖製範齋襯築糧) = 醖鏇艱憲衊餘積積夢鑰膚鏇艱鑰蓋範糧鹹襯製 (築艱襯窪鹹範網鏇夢製 ) 更多	积极	2018-04-10
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	糧窪選醖選淵艱夢獵遞(築築遞衊齋壓網壓齋繭) = 簾構範鹽鏇蓋簾繭鬱憲遞鑰壓蓋鑰憲餘簾壓選 (網膚壓觸觸窪糧觸築範, 10.8 ~ 20.0)	积极	2016-06-01
				5-fluorocytosine+subgroup from an external control	-
ASCO2016 人工标引	临床1期	胶质母细胞瘤	-	Toca511/Toca-FC	繭廠構繭選願鏇夢選鹹(膚鹹鏇壓膚齋膚網觸獵) = 餘鏇網壓齋繭醖範壓淵築壓膚淵蓋鏇餘繭顧蓋 (窪齋鏇顧淵壓願蓋鏇蓋 )	积极	2016-05-20
				lomustine	繭廠構繭選願鏇夢選鹹(膚鹹鏇壓膚齋膚網觸獵) = 選構獵鑰遞遞遞醖艱蓋築壓膚淵蓋鏇餘繭顧蓋 (窪齋鏇顧淵壓願蓋鏇蓋 )