A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus

This is a Phase I study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.

开始日期2024-02-02

申办/合作机构

Autolus Ltd.

NCT06173518 / Recruiting临床1期

A Single-Arm, Open-Label, Multi-Centre, Phase Ib Study Evaluating the Safety and Preliminary Efficacy of AUTO1 in Pediatric Patients With CD19-Positive Relapsed/ Refractory (r/r) B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B Cell Non-Hodgkin Lymphoma (B NHL)

This is a Phase Ib study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 in pediatric patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B ALL) and r/r B cell Non-Hodgkin lymphoma (B NHL)

开始日期2023-11-16

申办/合作机构

Autolus Ltd.

ACTRN12621000762853 / Recruiting临床1期

Phase I Clinical Trial of MB.CART19.1 CD19 Chimeric Antigen Receptor (CAR)T Cells in Relapsed or Refractory CD19-Positive Haematological Malignancy

开始日期2021-07-21

申办/合作机构

Metro North Hospital & Health Service

100 项与 Obecabatagene autoleucel 相关的临床结果

登录后查看更多信息

100 项与 Obecabatagene autoleucel 相关的转化医学

登录后查看更多信息

100 项与 Obecabatagene autoleucel 相关的专利（医药）

登录后查看更多信息

159

项与 Obecabatagene autoleucel 相关的文献（医药）

2024-12-01·American Journal of Hematology

Toxicities and outcome after CD19‐directed chimeric antigen receptor T‐cell therapy for secondary neurolymphomatosis

Article

作者: Doubrovinskaia, Sofia ; Abramson, Jeremy S. ; Hochberg, Ephraim P. ; Kaulen, Leon D. ; Barnes, Jeffrey A. ; Wick, Wolfgang ; Chen, Yi‐Bin ; Soumerai, Jacob D. ; Choi, Bryan D. ; Frigault, Matthew J. ; El‐Jawahri, Areej ; Shankar, Ganesh ; Maus, Marcela V. ; Martinez‐Lage, Maria ; Karschnia, Philipp ; Dietrich, Jorg ; Johnson, P. Connor

Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. Neurolymphomatosis patients treated with CD19 CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification, management, and response rates were recorded. Eleven neurolymphomatosis patients were identified with a median of 2 lines of PNS-directed treatments (range: 1-3) prior to receiving CD19-CAR T-cells. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome (CRS) was detected in 8/11 (73%; grade 1: N = 7; grade 2: N = 1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome (ICANS) were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. CRP levels at infusion were predictive of ICANS (area under the curve: 0.96, p = 0.01). Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions (CR) were achieved in three cases (27%), with 2 patients in sustained CR nine and 46 months after CD19-CAR infusion. Median progression-free survival (PFS) was 4 months. Collectively, CD19-CAR T-cell treatment was well tolerated and showed promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier. Toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.

2024-12-01·Current Research in Translational Medicine

Point of care CD19 chimeric antigen receptor (CAR) T-cells for relapsed/refractory acute myeloid leukemia (AML) with aberrant CD19 antigen expression

Article

作者: Jacoby, Elad ; Shem-Tov, Noga ; Itzhaki, Orit ; Shouval, Roni ; Avigdor, Abraham ; Danylesko, Ivetta ; Yerushalmi, Ronit ; Toren, Amos ; Nagler, Arnon ; Shimoni, Avichai

Relapsed/refractory (r/r) acute myeloid leukemia (AML) is associated with poor prognosis. CD19 is a B-cell marker, is aberrantly expressed in AML, mostly with t(8; 21)(q22; q22.1). Here we report the results of a phase 2 study giving point of care produced CD19 CAR T- cells for r/r AML with aberrant expression of CD19 (NCT04257175). Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28. Six patients (5 adults and 1 child) were included. Median number of previous chemotherapy lines was 4 (range, 3-8) and four patients received CAR T-cells 8-18 months post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cytokine release syndrome (CRS) of any grade occurred in all patients, and 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients at low grades. Tocilizumab was administered to 2 patients and corticosteroids to 3 patients. Four patients achieved a complete remission (CR), while 2/6 progressed (PD). Three patients (2 with CR and 1 with PD) underwent allo-HSCT (it was the second transplant in 2) 2-5 months post CAR T-cells infusion. The median duration of response in patients achieving CR was 8.5 (range; 3-14) months. However, all patients eventually died within 5 (1-18) months. In conclusion, CD19 CAR T- cell treatment for AML is feasible and safe. However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.

2024-09-01·MedComm

Targeting chronic lymphocytic leukemia with B‐cell activating factor receptor CAR T cells

Article

作者: Luo, Yan ; Li, Shuhua ; Qie, Yaqing ; Murthy, Hemant S. ; Gadd, Martha E. ; Qin, Hong ; Rivera‐Valentin, Rocio ; Yassine, Farah ; Liu, Andrew ; Dronca, Roxana ; To, Tommy ; Shao, Qing ; Kharfan‐Dabaja, Mohamed A.

AbstractThe challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T‐cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T‐cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B‐cell activating factor receptor (BAFF‐R) as a promising target for CAR design against CLL. BAFF‐R is essential for B‐cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF‐R CAR T‐cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19‐knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF‐R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient‐derived CAR T cells against autologous tumor cells. Given these promising results, BAFF‐R CAR T‐cell therapy has the potential to meet the long‐standing need for an effective treatment on CLL patients.

159

项与 Obecabatagene autoleucel 相关的新闻（医药）

2024-11-16

·药明康德

一次治疗5年有效的基因疗法获FDA批准上市；使致命脑瘤患者肿瘤细胞完全消失的CAR-T疗法…… | 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。美国FDA批准首个直接注入大脑的基因疗法Kebilidi，用于治疗芳香族L-氨基酸脱羧酶缺乏症（AADCD）。美国FDA批准了首个无需风险评估缓解策略计划（REMS）的嵌合抗原受体（CAR）-T细胞疗法Aucatzyl，用于治疗复发或难治性B细胞急性淋巴细胞白血病（r/r B-ALL）的成年患者。斯坦福大学医学院团队开发的CAR-T细胞疗法使1名患有治疗致命脑瘤的患者已获得了持续30多个月的完全缓解（CR）。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✦——— ◇ PTC Therapeutics公司宣布，美国FDA加速批准基因疗法Kebilidi（eladocagene exuparvovec）用于治疗芳香族L-氨基酸脱羧酶缺乏症的儿童和成人患者，无论他们的疾病严重程度为何。AADCD患者由于编码AADC酶的DDC基因出现变异，导致AADC酶功能缺失，因此患者无法合成运动功能所必需的神经递质多巴胺。根据新闻稿，这是FDA批准的首个直接注射到大脑的基因疗法。 Kebilidi是一种基于腺相关病毒2（AAV2）载体的基因疗法，旨在通过一次性治疗，将功能正常的DDC基因直接递送到大脑的壳核中，提高AADC酶的水平并恢复多巴胺的生产。该疗法通过立体定向神经外科手术直接施用于大脑壳核。临床试验结果表明，患者在接受该基因治疗后，多巴胺会从头合成，随后逐渐获得运动发育里程碑。2022年，它首次获得欧盟委员会批准上市（商品名Upstaza），成为直接注入大脑的首款获批基因疗法，也是改变AADCD疾病进程的首款获批疗法。 ◇ Autolus Therapeutics公司宣布，美国FDA已批准Aucatzyl（obecabtagene autoleucel，obe-cel）用于治疗复发或难治性B细胞急性淋巴细胞白血病的成年患者。Aucatzyl是一款靶向CD19抗原的自体CAR-T细胞疗法。它旨在克服当前CAR-T细胞疗法在临床活性和安全性方面的局限性。它的独特之处在于，设计的CAR在与CD19结合后具有较快的解离速度（fast off-rate），从而能够尽量减少T细胞的过度激活，在降低毒副作用的同时，不易发生T细胞耗竭，提高CAR-T疗法的持久性。根据新闻稿，Aucatzyl是获美国FDA批准的首个无需风险评估缓解策略计划的CAR-T疗法。此次美国FDA的批准主要是基于Aucatzyl在r/r B-ALL成人患者中所进行的FELIX临床试验的结果。65名疗效可评的患者中，总CR率为63%，其中包括51%的患者在任何时间达成CR，12%患者在任何时间达成CR伴不完全的血液学恢复（CRi）。此外，主要疗效终点是在3个月内达成CR，共有42%的患者达成，中位缓解持续时间（DOR）为14.1个月。安全性方面，Aucatzyl表现出低水平的细胞因子释放综合征（CRS），3级事件发生率为3%，无4级或5级事件。7%的患者出现≥3级免疫效应细胞相关神经毒性综合征（ICANS）。 ◇ Adaptimmune Therapeutics公司公布了其关键性2期IGNYTE-ESO试验的主要分析数据，该试验评估其在研细胞疗法lete-cel在之前接受过蒽环类药物治疗的晚期滑膜肉瘤或黏液样/圆细胞脂肪肉瘤（MRCLS）患者中的疗效与安全性。独立审评结果显示，27/64（42%）的患者达成根据RECIST v1.1标准的缓解，其中6例为CR，21例为部分缓解（PR）。患者的中位DOR为12.2个月（95% CI：6.8，19.5），中位无进展生存期（PFS）为5.3个月（95% CI：4.0，8.0）。 Lete-cel是一种靶向NY-ESO-1实体瘤抗原的工程化T细胞受体（TCR）-T细胞疗法。NY-ESO-1在滑膜肉瘤和MRCLS细胞中高度表达，该蛋白通过HLA-A*02呈现。基于所公布的积极数据，Adaptimmune计划在2025年底前启动lete-cel的生物制品许可申请（BLA）滚动提交，用于治疗晚期或转移性滑膜肉瘤和MRCLS。 ◇ 近日，《柳叶刀》（The Lancet）杂志上发表了使用经改良优化的基因疗法betibeglogene autotemcel（beti-cel）治疗严重输血依赖型β地中海贫血患者的疗效和安全性结果。Beti-cel是一款已上市的基因疗法，于2022年8月在美国获批上市。在两项1/2期beti-cel的研究中，研究人员发现非β0/β0基因型患者中约79%可“摆脱”输血依赖，而大多数β0/β0基因型患者（63%）仍存在输血依赖，不同基因型β地中海贫血患者结局之间的差异，提示需改良细胞生产技术，增加载体拷贝数，改善转导的造血干细胞质量和产量。研究人员将beti-cel进行了改良优化，使用BB305慢病毒载体转导以提高转导效率。在一项3期临床试验中，改良的beti-cel使89%（16/18）不同基因型的严重输血依赖型β地中海贫血患者摆脱输血依赖，效果维持至少3年多，有望使患者血红蛋白水平接近正常，且无异基因自体造血干祖细胞（HSPC）移植风险和局限性。该研究结果表明，改良的beti-cel有望成为β地中海贫血患者的潜在治愈方式。 ◇ Neurogene公司公布了其用于治疗Rett综合征的基因疗法NGN-401在1/2期临床试验中的积极中期数据。截至2024年10月17日的数据，所有受试者在临床医生评定的临床总体印象改善量表（CGI-I）上与基线水平相比提高了2分。所有受试者在护理者填写的Rett综合征行为问卷（RSBQ）上有所改善，与基线水平相比改善了28%-52%不等。所有在基线时有睡眠障碍、便秘和吞咽困难的受试者都表现出客观的改善。技能和发育里程碑方面的进步是一致的、持久的，并且随着时间的推移而加深，显示出超出自然病程预期的改善。此外，低剂量NGN-401具有良好的耐受性和有利的安全性。 NGN-401是一种在研AAV基因疗法，递送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，能够实现目标水平的MECP2转基因表达，而不会引起与传统基因治疗相关的过表达相关毒性。 ◇ Fate Therapeutics公司公布了其靶向人表皮生长因子受体2（HER2）的多重工程化CAR-T细胞疗法FT825/ONO-8250的初步临床数据。在一项正在进行的1期研究中，3名既往接受过大量治疗的晚期实体瘤患者接受了低剂量的FT825/ONO-8250治疗，没有观察到剂量限制性毒性（DLT）和任何级别的CRS、ICANS或移植物抗宿主病（GvHD）。在治疗后第8天观察到CAR-T细胞扩增峰值，并且患者外周血的FT825/ONO-8250表型表明CAR-T细胞处于激活状态，没有耗竭的证据。 ◇ 近日，斯坦福大学医学院的研究团队在《自然》杂志上发表了一项研究，公布了使用GD2（一种二唾液酸神经节苷脂）靶向CAR-T细胞疗法治疗致命脑和脊髓肿瘤儿童患者的1期临床研究的积极结果。11名患有H3K27M突变型弥漫性内源性脑桥胶质瘤（DIPG）或脊髓弥漫性中线胶质瘤（sDMG）的患者接受了GD2-CART治疗，9例患者因疾病引起的神经功能残疾获得了改善，4名患者表现出显著的肿瘤体积缩小（52%、54%、91%和100%），3名患者的肿瘤体积有较小的缩小。其中一名患者自入组后已获得了持续30多个月的CR。 ◇ Next Generation Gene Therapeutics（NGGT）公司宣布其用于治疗苯丙酮尿症（PKU）的在研基因疗法NGGT002在中国进行的研究者发起的试验（IIT）中的积极数据。接受高剂量NGGT002的6名患者中有5名在给药3周后血浆苯丙氨酸水平恢复至正常范围内。首位接受NGGT002给药的患者在给药后40周，血浆苯丙氨酸水平持续保持在正常范围内。目前，该疗法已在中国和美国启动1/2期临床试验，以评估其治疗成人PKU患者的安全性和有效性。 ◇ Atamyo Therapeutics公司宣布，美国FDA已批准其一次性AAV基因疗法ATA-200的IND申请，可针对γ-肌聚糖蛋白相关肢带型肌营养不良2C/R5型（LGMD2C/R5）患者开展1b/2b期临床试验。γ-肌聚糖蛋白是一种跨膜蛋白，参与肌肉纤维与其周围组织的连接。LGMD2C/R5是一种罕见的遗传病，由γ-肌聚糖蛋白基因的突变引起。ATA-200能提供一个正常的基因拷贝，以产生γ-肌聚糖蛋白。在临床前小鼠模型中，ATA-200证明了其耐受性和纠正病症及病理生物标志物的能力。该公司计划在2024年第四季度开始招募患者。 ◇ 精准生物自主研发的CD19靶向CAR-T细胞疗法pCAR-19B（普基仑赛注射液）的2期临床研究数据入选美国血液学会（ASH）年会口头报告。数据显示，普基仑赛注射液针对中国3~21岁儿童和青年CD19阳性r/r B-ALL患者，最佳客观缓解率（ORR）达90.63%。根据ASH官网的公示，该研究代表了亚洲人群中首个儿童B-ALL的关键临床试验，有望为中国儿童和青少年r/r B-ALL患者提供了一种新的治疗选择。目前，普基仑赛注射液的新药上市申请已经获中国国家药品监督管理局（NMPA）受理，并被纳入优先审评，用于治疗3～21岁儿童和青少年CD19阳性的r/r B-ALL患者。精准生物此前新闻稿介绍，该产品有望成为中国首款针对儿童白血病的CAR-T产品。 ◇ 中国国家药监局药品审评中心（CDE）官网公示显示，来恩生物自主研发的GZL-016注射液获临床试验默示许可，适应症为乙肝病毒相关肝细胞癌。GZL-016注射液是一种自体T细胞疗法，通过mRNA编码表达靶向乙肝病毒（HBV）表面抗原的TCR，赋予T细胞特异性识别并杀伤乙肝病毒相关肝细胞癌的能力。GZL-016注射液通过有效利用mRNA瞬时表达的特性，结合多次输注的方式，可很好地控制安全性并维持疗效。此外，患者在治疗前无需清淋，进一步提高了患者用药的安全性和可及性。新闻稿指出，GZL-016注射液是全球首个针对HBV的mRNA编码TCR-T细胞疗法，也是来恩生物继取得美国FDA和新加坡卫生科学局（HSA）默示许可后的又一重要成果。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ Nippon Shinyaku公司和Atsena Therapeutics公司就Atsena公司的潜在“first-in-class”基因疗法ATSN-101在美国的商业化以及在日本的开发和商业化签订了独家许可协议。ATSN-101是一种以AAV5为载体的基因治疗药物，通过视网膜下注射将功能性的人类GUCY2D基因引入光感受器，用于治疗因GUCY2D双等位基因突变引起的Leber先天性黑蒙。ATSN-101已获得美国FDA授予的罕见儿科疾病认定、再生医学先进疗法认定和孤儿药资格，用于治疗GUCY2D相关LCA1。根据许可协议的条款，Nippon Shinyaku公司将获得ATSN-101在美国和日本的独家商业权利，而Atsena公司将保留世界其他地区的商业权利。Atsena Therapeutics公司将获得预付款以及额外的里程碑付款。 ◇ Vittoria Biotherapeutics公司宣布完成了2500万美元的私募融资，本轮融资是在2023年11月获得的1500万美元融资基础上追加的1000万美元。新闻稿指出，这笔资金将主要用于支持其主要肿瘤候选药物VIPER-101的1期临床试验。 VIPER-101是一种自体、删除CD5的基因编辑细胞疗法，用于治疗T细胞淋巴瘤患者。85%以上的T细胞淋巴瘤患者的癌细胞都存在CD5。VIPER-101利用公司专有的Senza5平台技术，通过基因编辑消除CD5介导的免疫抑制，从而增强T细胞的效应功能。在临床前研究中，VIPER-101已显示出优于传统CD5靶向CAR-T细胞的疗效。 ◇ 中盛溯源完成1.5亿元B轮融资，将加速推进诱导多能干细胞（iPSC）治疗领域多款临床管线的临床开发，以及后续产品商业化。围绕iPSC核心技术，该公司在抗炎修复、肿瘤免疫和再生医学三大医学方向上，将多条细胞药物管线推进至注册临床开发阶段。截止目前，已有1条iPSC来源的间充质干细胞（iMSC）和2条iPSC来源的自然杀伤细胞（iNK）管线处于1/2期临床试验，另有帕金森病和糖尿病等多条产品管线将陆续进入注册临床试验。 ◇ 康霖生物宣布完成1.5亿元A轮融资。该公司成立于2015年，专注于基因治疗创新药的研发和商业化，针对的领域多为严重影响人类健康的疾病，如地中海贫血症、艾滋病、血友病和帕金森病等。KL003细胞注射液是康霖生物的核心产品，为一款基因修饰自体造血干细胞产品，拟开发用于治疗成人或儿童输血依赖型β-地中海贫血症。KL003于2024年1月获得NMPA的批准开展临床试验，目前已经完成1期临床全部患者的入组工作。 ◇ 莱芒生物宣布完成超亿元A轮融资首关，所得资金将主要用于极低剂量代谢增强型CAR-T细胞药物IND申报、自动化生产工艺研发，以及加速推进代谢增强型实体瘤细胞治疗药物的临床转化。该公司新闻稿指出，其进展最快的在研管线为代谢增强型CD19 CAR-T疗法（Meta10-19注射液）。在一项IIT中，该疗法以极低的给药剂量（低至传统CAR-T疗法剂量的1%）实现了肿瘤细胞的完全清除，成功帮助超过20名复发难治性白血病或淋巴瘤患者达到CR状态并顺利出院。在最新的IIT临床研究中，临床专家将代谢增强型CD19 CAR-T疗法的注射剂量进一步降低至常规剂量的千分之一后仍然能够在患者体内高效扩增，并成功助力数位患者获得CR。莱芒生物还将启动针对实体瘤的代谢增强型细胞治疗临床研究，以期彻底改变细胞治疗对实体瘤疗效欠佳的现状。 ▲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] PTC Therapeutics Announces FDA Approval of AADC Deficiency Gene Therapy. Retrieved November 13, 2024 from https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-fda-approval-of-aadc-deficiency-gene-therapy-302304880.html [2] Monje, M., Mahdi, J., Majzner, R. et al. Intravenous and intracranial GD2-CAR T cells for H3K27M diffuse midline gliomas. Nature (2024). https://doi.org/10.1038/s41586-024-08171-9+ [3] Autolus Therapeutics Announces FDA Approval of AUCATZYL® (obecabtagene autoleucel – obe-cel) for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Retrieved November 8, 2024 from https://www.globenewswire.com/news-release/2024/11/08/2977884/0/en/Autolus-Therapeutics-Announces-FDA-Approval-of-AUCATZYL-obecabtagene-autoleucel-obe-cel-for-adults-with-relapsed-refractory-B-cell-acute-lymphoblastic-leukemia-r-r-B-ALL.html [4] Kwiatkowski JL, Walters MC, Hongeng S, Yannaki E, Kulozik AE, Kunz JB, Sauer MG, Thrasher AJ, Thuret I, Lal A, Tao G, Ali S, Thakar HL, Elliot H, Lodaya A, Lee J, Colvin RA, Locatelli F, Thompson AA. Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial. Lancet. 2024 Nov 8:S0140-6736(24)01884-1. doi: 10.1016/S0140-6736(24)01884-1. Epub ahead of print. PMID: 39527960. [5] Next Generation Gene Therapeutics (NGGT) Announces Positive New Data on NGGT002 for the Treatment of Phenylketonuria (PKU). Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/next-generation-gene-therapeutics-nggt-announces-positive-new-data-on-nggt002-for-the-treatment-of-phenylketonuria-pku-302300911.html [6] Fate Therapeutics Highlights Cancer-selective, HER2-Targeting Profile of FT825 / ONO-8250 CAR T-cell Product Candidate for Treatment of Advanced Solid Tumors at 2024 SITC Annual Meeting. Retrieved November 15, 2024, from https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-cancer-selective-her2-targeting [7] Neurogene Reports Positive Interim Efficacy Data from First Four Low-Dose Pediatric Participants in NGN-401 Gene Therapy Clinical Trial for Rett Syndrome. Retrieved November 15, 2024, from https://ir.neurogene.com/news-releases/news-release-details/neurogene-reports-positive-interim-efficacy-data-first-four-low [8] IND for ATA-200, a Gene Therapy for the Treatment of Limb-Girdle Muscular Dystrophy Type 2C/R5 (LGMD2C/R5), cleared to proceed by FDA. Retrieved November 15, 2024, from https://www.businesswire.com/news/home/20241112690214/en/IND-for-ATA-200-a-Gene-Therapy-for-the-Treatment-of-Limb-Girdle-Muscular-Dystrophy-Type-2CR5-LGMD2CR5-cleared-to-proceed-by-FDA [9] 4205 A Phase 2 Clinical Trial of Anti-CD19 CAR-T (pCAR-19B) in Chinese Pediatric and Young Adult with Relapsed/Refractory (R/R) CD19+ B-ALL: The First Pivotal Study in an Asian Population. Retrieved November 15, 2024, from https://ash.confex.com/ash/2024/webprogram/Paper206408.html [10] Vittoria Biotherapeutics Completes $25 Million in Private Financing to Propel Groundbreaking Cell Therapy Candidates. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/12/2978833/0/en/Vittoria-Biotherapeutics-Completes-25-Million-in-Private-Financing-to-Propel-Groundbreaking-Cell-Therapy-Candidates.html [11] 莱芒生物完成超亿元A轮融资首关，加速推进代谢增强型免疫疗法临床转化. Retrieved November 15, 2024, from https://mp.weixin.qq.com/s/cT-tzg1d0nURECS8xohd3A [12] Adaptimmune's Lete-cel Achieves Primary Endpoint in Pivotal Trial. Retrieved November 13, 2024 from https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/277/adaptimmunes-lete-cel-achieves-primary-endpoint-in-pivotal [13] 全球首个！来恩生物mRNA编码TCR-T获批临床，精准攻克肝细胞癌. Retrieved November 15, 2024 from https://mp.weixin.qq.com/s/0BvwbitxvT2hc4isp0qryg [14] Nippon Shinyaku and Atsena Therapeutics enter into an Exclusive Strategic Collaboration for ATSN-101 in the U.S. and Japan. Retrieved November 15, 2024 from https://www.globenewswire.com/news-release/2024/11/13/2979922/0/en/Nippon-Shinyaku-and-Atsena-Therapeutics-enter-into-an-Exclusive-Strategic-Collaboration-for-ATSN-101-in-the-U-S-and-Japan.html 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

细胞疗法上市批准基因疗法免疫疗法

2024-11-14

·PRNewswire

Kyverna Therapeutics Announces New Patient Data Highlighting Potential of KYV-101 for Treatment of Lupus Nephritis in Symposium at ACR Convergence 2024

Positive Sustained Efficacy and Durability at >6-month Follow-Up Observed in Patients With Severe Lupus Nephritis (LN) Treated With KYV-101 Target Dose KYV-101 Treatment Continues to Demonstrate Robust Safety and Tolerability With No High-Grade CRS or ICANS Observed EMERYVILLE, Calif., Nov. 14, 2024 /PRNewswire/ -- Kyverna Therapeutics, Inc. (Kyverna), a clinical-stage biopharmaceutical company focused on developing cell therapies for patients with autoimmune diseases, announces today that it will present updated clinical data from LN patients treated with KYV-101 in ongoing Kyverna-sponsored KYSA-1 and KYSA-3 Phase 1/2 studies and named patient treatments. Kyverna, alongside leading academic collaborators, will highlight all six patients treated with the target dose of 1×108 CD19 CAR T cells, four of which have at least six months of follow-up. All patients at six months of follow-up after treatment at the target dose continue to display sustained efficacy and durability across numerous key clinical measures. These updates will be presented at a company symposium titled, "KYV-101 Anti-CD19 CAR T-Cell Therapy: The Future of Autoimmune Disease Treatment," to be held at 5:45 pm ET on November 18, 2024. Slides from the presentation will be posted to the company website following the symposium. "Lupus nephritis patients encounter a tremendous burden of disease associated with high morbidity and mortality, with up to 30% of patients ultimately experiencing end-stage renal disease that requires dialysis or kidney transplant," said Prof. Georg Schett, M.D. from the Friedrich-Alexander-University in Erlangen, Germany, and one of the presenters. "The data reinforce that treatment with KYV-101 drives deep B cell depletion in patients with LN, and appears to reset the immune system, stabilize eGFR, preserve kidney function and enable clinical improvement in SLE activity. Notably, this clinical benefit is occurring while also eliminating immunosuppressants and reducing glucocorticoids to physiologic levels with a manageable safety profile." "As our KYV-101 clinical datasets mature, we are increasingly able to focus on the right patients, treated at the right dose, with the right protocol. We are excited to share these new data, which continue to reinforce KYV-101's potential for durable and life-changing outcomes in lupus nephritis patients, including those with high chronicity and disease severity," said Warner Biddle, Chief Executive Officer at Kyverna. Additional Updates: Also at ACR Convergence 2024, Kyverna will present data on next-generation approaches, most notably with a poster on Ingenui-T, the Company's preclinical 3-day manufacturing process using autologous whole blood as starting material. Ingenui-T is designed to improve the patient experience by eliminating apheresis, leading to a potential for improved convenience, access and overall cost reduction. As the poster highlights, drug product from the Ingenui-T process manufactured with whole blood from patients with SLE or healthy donors displayed product characteristics similar to KYV-101. In addition, results from collaborative work on the molecular mechanisms underlying immune reset through deep B-cell depletion with CD19 CAR T-cell therapy performed in collaboration with Verily Life Sciences, an Alphabet precision health company, and the University of Erlangen will be shared as an oral presentation. The posters and slides from the oral presentation at ACR Convergence 2024 will be available on the publications page of Kyverna's website. About Lupus Nephritis (LN) Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), more commonly known as lupus. Approximately 40 percent of adults diagnosed with lupus eventually develop LN and 60 percent or more of LN patients will fail standard of care and approved treatments1,2. Aside from modest efficacy, current treatments expose these young adults to the well-demonstrated detrimental consequences of chronic treatment with corticosteroids and other powerful immunosuppressants. Up to 30 percent of patients with LN will develop kidney failure, requiring dialysis or a kidney transplant to stay alive3 . About KYV-101 KYV-101 is an autologous, fully human CD19 CAR T-cell product candidate for use in B cell-driven autoimmune diseases. The CAR in KYV-101 was designed by the National Institutes of Health (NIH) to improve tolerability and tested in a 20-patient Phase 1 trial in oncology. Results were published by the NIH in Nature Medicine4. KYV-101 is currently being evaluated in sponsored, open-label, Phase 1/2 and Phase 2 trials in the United States and Germany across two broad areas of autoimmune diseases, rheumatologic and neuroinflammatory, as well as in investigator-initiated trials for multiple indications in multiple geographies. The clinical experience to date with KYV-101 in both oncological and autoimmune diseases highlights the differentiated properties of KYV-101 and the potential to treat autoimmune patients. About Kyverna Therapeutics Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases. Our lead CAR T-cell therapy candidate, KYV-101 is advancing through clinical development with sponsored clinical trials across two broad areas of autoimmune disease: rheumatology and neurology, including Phase 2 trials for stiff-person syndrome, multiple sclerosis and myasthenia gravis, a Phase 1/2 trial for systemic sclerosis, and two ongoing multi-center Phase 1/2 trials in the United States and Germany for patients with lupus nephritis. Kyverna's pipeline includes next-generation CAR T-cell therapies in both autologous and allogeneic formats with properties intended to be well suited for use in B cell-driven autoimmune diseases. For more information, please visit . Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." The words, without limitation, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these or similar identifying words. Forward-looking statements in this press release include, without limitation, those related to: the potential impact of the clinical outcomes from the ongoing clinical programs; the potential impact of the new data on the treatment efficacy and safety profile of KYV-101; the potential that the results of the ongoing trials could drastically change the treatment landscape for the targeted autoimmune diseases; Kyverna's goals to develop certain paradigm-shifting treatment options; the potential for KYV-101 to provide durable, immunosuppressant-free remission for autoimmune disease patients; Kyverna's beliefs about the differentiated properties of KYV-101; and Kyverna's clinical trials and named-patient activities. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties related to market conditions, and other factors discussed in the "Risk Factors" section of Kyverna's most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q that Kyverna has filed or may subsequently file with the U.S. Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of Kyverna's management team and speak only as of the date hereof, and Kyverna specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Contact: Consort Partners for Kyverna: [email protected] Investors: [email protected] Media: [email protected] 1Anders et al., Nat Rev Dis Primers. 2020; 6:7. 2Parodis et al., Autoimmun Rev. 2024; 23:103418. 3Lateef and Petri, Arthritis Res & Ther. 2012; 14(Suppl 4):S4. 4Brudno et al., Nature Medicine. 2020; 26:270-280. SOURCE Kyverna Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

细胞疗法临床1期临床2期免疫疗法临床结果

2024-11-14

·佰傲谷BioValley

CAR-T价格新高

昨日，Autolus Therapeutics宣布，美国FDA已经批准Aucatzyl（obecabtagene autoleucel，obe-cel），用于治疗复发性/难治性成人B细胞急性淋巴细胞白血病（r/r B-ALL）的成人患者。延伸阅读：“连环杀手”CAR-T即将上市，向Tecartus发起挑战 Aucatzyl是美国FDA批准的第五款CD19 CAR-T，其获批适应症与吉利德的Tecartus完全对上。而且根据报道，Aucatzyl的定价为52.5万美元，比Tecartus的价格要高上一大截，作为一款后发的药物，凭啥定更高的价。另外，52.5万美元/剂的Aucatzyl是目前全球获批CAR-T细胞治疗产品中，单价最高的一位。（CAR-T价格目录在文末）更高的安全性 Autolus一直以来，都以“更高的安全性”作为Aucatzyl的卖点。在一个电话会议上，Autolus的首席运营官Christopher Vann对于Aucatzyl的价格高于Tecartus这样解释道：“我们相信，这一定价反映了我们迄今为止观察到的临床证据和益处，以及差异化的安全性，这为医疗保健系统带来了有意义的经济益处。” Aucatzyl是一款自体的、靶向CD19的CAR-T细胞疗法，其被设计为具有快速的靶点解离率（target binding off-rate），以减少工程化T细胞的过度激活，被设计的更类似天然存在的T细胞，同时能够提高对目标细胞的连续杀伤能力。 Aucatzyl的批准是基于FELIX临床研究结果，94名患者接受了至少一次Aucatzyl输注，其中65例患者在筛查和清淋前骨髓中原始细胞>5%，接受了合格产品后具有了可评估的疗效。在疗效可评估的患者中（n=65），63%的患者达到了总体完全缓解（OCR），包括51%的CR和12%的CRi。主要疗效指标为3个月内完全缓解，42%的患者达到，中位缓解持续时间（DOR）为14.1个月。 Aucatzyl显示低水平的细胞因子释放综合征（CRS），有3%的3级事件，无4级或5级事件。7%的患者报告了≥3级免疫效应细胞相关神经毒性综合征（ICANS）。FDA没有对Aucatzyl的REMS要求。Aucatzyl的安全性包括对CRS、神经毒性和继发性血液系统恶性肿瘤的黑框警告。值得注意的是，Aucatzyl是第一个被批准的无需风险评估缓解策略（REMS）的CAR-T疗法。REMS是美国FDA为管理某些药品或生物制品（特别是CAR-T）的已知或潜在严重风险，而要求制药公司制定并实施的一系列措施和干预手段，旨在帮助减少特定严重不良事件的发生或严重程度，确保治疗益处大于风险，并安全有效地使用。令人担忧的销售前景尽管Autolus在吹捧Aucatzyl的安全性和疗效。以及扩大Aucatzyl在全球市场的批准。目前，欧盟和英国的监管机构正在审查obe-cel的上市申请。但是小编仍然不看好Aucatzyl的销售前景。首先，作为Tecartus的竞争对手，Aucatzyl在市场优先性、治疗网点、价格上都没有优势，疗效也差不多，只有安全性突出一些。其次，Tecartus自2021年获得第二个批准用于治疗B-ALL，经历了近4年的销售增长，也来到了瓶颈期，卖不太动了。根据吉利德财报，Tecartus的2024Q3单季度销售额为9800万美元，同比增长2%，环比下滑近9%。说明B-ALL这个市场份额基本上已经被Tecartus消耗的差不多了，这时候Aucatzyl才入局。小编还是不太看好Aucatzyl的销售前景。延伸阅读：低价CAR-T 如有错漏，欢迎留言补充参考资料： 1.https://www.globenewswire.com/news-release/2024/11/08/2977884/0/en/Autolus-Therapeutics-Announces-FDA-Approval-of-AUCATZYL-obecabtagene-autoleucel-obe-cel-for-adults-with-relapsed-refractory-B-cell-acute-lymphoblastic-leukemia-r-r-B-ALL.html 2.https://www.biopharmadive.com/news/autolus-fda-approval-aucatzyl-obe-cel-car-t/732543/ 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · · · · · · ·

细胞疗法免疫疗法临床结果上市批准ASH会议

100 项与 Obecabatagene autoleucel 相关的药物交易

登录后查看更多信息

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
前体B细胞急性淋巴细胞白血病	美国	Autolus Ltd.	2024-11-08

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
复发性 B 细胞急性淋巴细胞白血病	申请上市	美国	Autolus Therapeutics Plc	2023-11-29
难治性 B 细胞急性淋巴细胞白血病	申请上市	美国	Autolus Therapeutics Plc	2023-11-29
前体B细胞急性淋巴细胞白血病	申请上市	英国	Autolus Therapeutics Plc	-
侵袭性 B 细胞非霍奇金淋巴瘤	临床1期	西班牙	Autolus Ltd.	2023-11-16
侵袭性 B 细胞非霍奇金淋巴瘤	临床1期	美国	Autolus Ltd.	2023-11-16
原发性中枢神经系统淋巴瘤	临床1期	英国	Autolus Ltd.	2022-01-30
慢性淋巴细胞白血病	临床1期	英国	University College London	2017-09-29
复发性成人急性淋巴细胞白血病	临床1期	英国	University College London	2017-09-29
小淋巴细胞淋巴瘤	临床1期	英国	University College London	2017-09-29
弥漫性大B细胞淋巴瘤	药物发现	英国	University College London	2016-06-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04404660 (FELIX, ASH2024)	临床1/2期	复发性成人急性淋巴细胞白血病 CD19	127	Obecabtagene autoleucel (obe-cel)	膚膚淵築醖鹹鬱壓憲糧(憲窪廠積鑰製願鬱構鹽) = 72 (70.6%) were CRS only 獵觸製製積壓襯願醖積 (鹽淵遞獵製築鹽淵獵醖 ) 更多	积极	2024-12-09
ASH2024	N/A	复发性 B 细胞急性淋巴细胞白血病	-	Obecabtagene autoleucel (obe-cel) (High-risk HT score)	網鑰繭鹹膚廠築網窪鹹(選獵餘淵壓糧鏇獵願膚) = 蓋窪淵夢膚構衊鬱積選積廠鹽衊鹽鏇壓憲網觸 (鹹鏇蓋網繭鏇衊醖窪壓, 34.6 ~ 55.6) 更多	-	2024-12-09
				Obecabtagene autoleucel (obe-cel) (Low-risk HT score)	網鑰繭鹹膚廠築網窪鹹(選獵餘淵壓糧鏇獵願膚) = 壓製鑰觸鏇獵窪襯網齋積廠鹽衊鹽鏇壓憲網觸 (鹹鏇蓋網繭鏇衊醖窪壓, 40.2 ~ 82.1) 更多
NCT04404660 (FELIX, ASH2024)	临床1/2期	复发性成人急性淋巴细胞白血病 ClonoSEQ®next-generation sequencing (NGS) assay	127	Obe-cel	(膚窪蓋齋艱壓膚襯襯糧) = 顧網廠獵築膚醖淵鏇鏇衊網鹹製鑰鏇餘製餘廠 (簾顧齋選夢顧壓鑰鹹鹽 ) 更多	积极	2024-12-09
NCT04404660 (FELIX, FDA_CBER) 人工标引	临床1/2期	前体B细胞急性淋巴细胞白血病	112	AUCATZYL (Efficacy Evaluable)	願選範鬱鬱蓋選鹽餘膚(構築糧糧顧蓋壓製網廠) = 餘廠壓繭鬱選願簾鑰淵觸艱鹽製鹹鏇網鑰鏇衊 (鑰鬱艱構積鬱蓋襯窪網, 50 ~ 75) 更多	积极	2024-11-08
				AUCATZYL (All Leukapheresed)	願選範鬱鬱蓋選鹽餘膚(構築糧糧顧蓋壓製網廠) = 憲憲鑰觸獵憲鏇糧築憲觸艱鹽製鹹鏇網鑰鏇衊 (鑰鬱艱構積鬱蓋襯窪網, 44 ~ 63) 更多
NCT04404660 (FELIX, SOHO2024)	临床1/2期	复发性成人急性淋巴细胞白血病	127	Obecabtagene Autoleucel (Obe-Cel) (Low TB)	憲鹹艱窪簾獵衊簾鹹衊(糧鬱醖窪遞繭淵壓鑰膚) = 鹽襯簾糧遞艱鑰餘齋選鑰築鏇衊積壓網襯觸簾 (糧製選淵鑰憲積夢製構, 1.527–2.802) 更多	积极	2024-09-04
				Obecabtagene Autoleucel (Obe-Cel) (High TB)	積襯鏇鑰積鑰遞糧製壓(積醖顧鑰憲選鏇鏇築衊) = 壓築壓鏇鬱醖範衊簾鬱鏇襯鹽糧廠廠鬱製淵餘 (鹽選衊遞遞範窪淵選艱 ) 更多
NCT04404660 (FELIX, ASCO2024) 人工标引	临床1/2期	复发性 B 细胞急性淋巴细胞白血病 \| 难治性 B 细胞急性淋巴细胞白血病 CD19 binder	127	Obe-cel	窪醖餘簾獵蓋鹽製齋築(範繭觸淵範鏇顧鑰製艱) = Pts who experienced B-cell recovery had a hazard risk of relapse or death 1.7 times compared with pts without B-cell recovery 齋餘艱築積襯築構積窪 (範蓋獵築鑰積鬱遞齋鹽 ) 更多	积极	2024-05-24
				Obe-cel (with censoring for consolidative SCT or new therapies)
NCT04404660 (FELIX, EHA2024) 人工标引	临床1/2期	前体B细胞急性淋巴细胞白血病	127	Obecabtagene autoleucel (obe-cel)	(構窪餘製願窪製願鏇淵) = 鏇鏇獵製夢選鹹積積築鹹構顧憲壓蓋膚製觸窪 (遞選簾廠獵願鑰網構鏇 ) 更多	积极	2024-05-23
NCT04404660 (FELIX, EHA2024) 人工标引	临床1/2期	复发性成人急性淋巴细胞白血病 \| 难治性成人急性淋巴细胞白血病	127	OBECABTAGENE AUTOLEUCEL (Bridging therapy with INO)	(齋夢選窪糧糧餘醖膚蓋) = 繭遞廠鏇積衊淵範餘膚製製夢鬱壓窪觸範蓋觸 (鏇糧繭獵餘遞衊糧構窪, 4.1 ~ NE) 更多	积极	2024-05-14
				OBECABTAGENE AUTOLEUCEL (Bridging therapy without INO)	(齋夢選窪糧糧餘醖膚蓋) = 觸餘範壓糧醖夢鑰齋齋製製夢鬱壓窪觸範蓋觸 (鏇糧繭獵餘遞衊糧構窪, 6.0 ~ NE) 更多
NCT04404660 (FELIX, EHA2024)	临床1/2期	难治性 B 细胞急性淋巴细胞白血病 CD19 chimeric antigen receptor (CAR)	127	OBECABTAGENE AUTOLEUCEL	繭製築蓋憲構顧糧範製(製廠製膚網糧鹽壓醖鹹) = 糧製鏇襯鹽蓋鬱積餘鑰選壓獵積積鬱鏇衊夢夢 (窪築繭淵憲膚憲淵鬱築 )	积极	2024-05-14
				OBECABTAGENE AUTOLEUCEL	繭製築蓋憲構顧糧範製(製廠製膚網糧鹽壓醖鹹) = 蓋鬱積鏇廠壓糧觸艱網選壓獵積積鬱鏇衊夢夢 (窪築繭淵憲膚憲淵鬱築 )
FELIX (ASH2023)	N/A	-	90	Obe-cel	糧選選艱簾襯窪鬱簾網(願糧襯鹹鹽憲膚觸網觸) = 遞鬱蓋淵齋網繭鹹繭淵鏇鑰願餘夢繭衊襯鹽網 (衊窪鏇築廠蓋網餘鏇襯 ) 更多	-	2023-12-11