Tabelecleucel

FDA lifts clinical hold enabling resumption of clinical trials FDA has granted a Type A Meeting to discuss path forward for BLA THOUSAND OAKS, Calif.--(BUSINESS WIRE)-- Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on Atara’s active Investigational New Drug (IND) applications for the EBVALLO™ (tabelecleucel) program. “We are very pleased to have addressed the FDA’s questions, and this has enabled the FDA to lift the clinical holds,” said Cokey Nguyen Ph.D., President and Chief Executive Officer of Atara. “We are working closely with our partner Pierre Fabre Laboratories and our clinical trial sites and anticipate resuming enrollment and treatment of patients as soon as possible.” In January 2025, the EBVALLO™ (tabelecleucel) program was placed on clinical hold. The clinical hold was directly linked to GMP compliance issues identified during the pre-license inspection of the third-party manufacturing facility referenced in the Complete Response Letter (CRL) for EBVALLO™ that was announced on January 16, 2025. The FDA has lifted the clinical hold on tabelecleucel after reviewing supplemental data on finished drug product. The Company is now allowed to restart the Phase 3 ALLELE clinical study for patients with Epstein-Barr Virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) and the Phase 2 label-expansion multi-cohort clinical study. The FDA has also granted a date for a Type A meeting to discuss the plan to address the issues raised by the FDA in the CRL from January 2025, and the path forward for resubmission of the EBVALLO™ BLA. “We are pleased that the FDA has granted our request for a Type A meeting and hope to gain clarity on the timing for resubmitting the tab-cel BLA for review by the FDA,” said Dr. Nguyen. Corporate Update Strategic Option Evaluation: As previously communicated, Atara engaged a well-known financial advisor to support a comprehensive process to explore and assess a range of potential strategic options for the Company. Alternatives may include, but are not limited to, an acquisition, merger, reverse merger, other business combinations, sale of assets, or other strategic transactions. We have temporarily paused this strategic option evaluation pending clarity with the FDA on timing of the resubmission of the EBVALLO™ BLA. It is possible that Atara may not pursue a strategic alternative or transaction or that any strategic alternative or transaction, if pursued, will not be completed on attractive terms, or that a strategic alternative or transaction may not ultimately be consummated. About Atara Biotherapeutics, Inc. Atara is harnessing the natural power of the immune system to develop off-the-shelf cell therapies for difficult-to-treat cancers and autoimmune conditions that can be rapidly delivered to patients from inventory. With cutting-edge science and differentiated approach, Atara is the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy. Our advanced and versatile T-cell platform does not require T-cell receptor or HLA gene editing and forms the basis of a diverse portfolio of investigational therapies that target EBV, the root cause of certain diseases, in addition to next-generation AlloCAR-Ts designed for best-in-class opportunities across a broad range of hematological malignancies and B-cell driven autoimmune diseases. Atara is headquartered in Southern California. For more information, visit atarabio.com and follow @Atarabio on X and LinkedIn. About tabelecleucel Tabelecleucel is an off-the-shelf allogeneic cell therapy composed of EBV specific cytotoxic T cell lymphocytes expanded from healthy donors and infused into partial HLA matched recipients suffering from EBV-driven malignancies such as post-transplant lymphoproliferative disease. Tab-cel is approved by the EMA, trademarked as EBVALLO™, for use in PTLD. Tab-cel is currently being evaluated in clinical studies and Atara is in the process of filing for approval by the FDA for commercial use in the United States. Pierre Fabre Laboratories holds worldwide Commercialization rights to EBVALLO™. Forward-Looking Statements This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: (1) the development, timing and progress of tab-cel, including the BLA and potential indications and the timing of resuming enrollment of the tab-cel clinical trials, the outcome of the Type A meeting with the FDA, the timing for FDA review of any resubmission of the BLA, and the potential characteristics and benefits of tab-cel; and (2) Atara’s exploration of strategic alternatives and ability to consummate one or more strategic transactions. Because such statements deal with future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; risks related to FDA feedback and the ability of Atara and its third-party manufacturer to address the issues identified in the CRL; our ability to access capital; the sufficiency of Atara’s cash resources and need for and ability to obtain additional capital on favorable terms or at all; risks and uncertainties related to Atara’s financial close and audit procedures; the timing of the strategic review process; whether Atara will pursue any strategic alternatives; in the event Atara pursues a strategic alternative, that the strategic alternative may not be attractive or ultimately consummated; whether any strategic alternative will result in additional value for Atara and its shareholders; whether the process will have an adverse impact on Atara; and other risks and uncertainties affecting Atara’s and its development programs, including those discussed in Atara’s filings with the Securities and Exchange Commission, including in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the Company’s most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250505744665/en/ Investor and Media Relations Amber Daugherty Sr. Director, Strategy and Operations adaugherty@atarabio.com Source: Atara Biotherapeutics, Inc. Released May 5, 2025

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。据不完全统计，2025年1-4月FDA共拒批了6款药物，“双艾疗法”和干眼症药物Reproxalap已不是首次在FDA碰壁。究其原因，其中有两款药物因CMC问题被拒批，两款药物因临床数据问题被拒批，一款药物因第三方问题被拒批。小编总结如下：Atara：Ebvallo2025年1月16日，Atara Biotherapeutics宣布美国FDA拒绝批准其细胞疗法Ebvallo（Tabelecleucel）的生物制品许可申请 (BLA)。该申请作为单一疗法治疗2岁及以上患有Epstein-Barr病毒阳性（EBV+）移植后淋巴细胞增殖性疾病（PTLD) 的成人和儿童患者，这些患者之前至少接受过一种疗法，包括含抗CD20的方案。根据新闻稿，本次未获得FDA批准仅与第三方生产商的检查结果有关。CRL中没有提及BLA中的生产工艺、临床疗效或临床安全性数据相关的缺陷，FDA也没有要求进行任何新的临床研究来支持Ebvallo的获批。Tab-cel是一种同种异体、“现货型” EBV特异性T细胞免疫疗法，可靶向并消除EBV 感染的细胞，除了用于治疗EBV阳性的移植后淋巴增殖性疾病，目前处在针对其他 EBV 相关的血液恶性肿瘤和实体瘤的早期开发阶段 。受此影响，Atara 股价暴跌40%。尽管如此，Atara还是寻求与FDA、Pierre Fabre实验室和第三方制造商合作，以实现Ebvallo在美国的获批。Atara的首席执行官Cokey Nguyen博士表示，对Ebvallo最终获批充满信心，重新申请后可能在六个月内获批。欧盟已于2022年12月授予EBVALLO上市许可。恒瑞医药：“双艾”疗法2025年3月21日，恒瑞医药公告称：收到FDA关于卡瑞利珠单抗联合甲磺酸阿帕替尼用于不可切除或转移性肝细胞癌患者一线治疗的生物制品许可申请的完整回复信。回复信中，FDA表示相关生产场地检查需进一步提交答复，但FDA并未在回复信中说明具体原因。韩国HLB公司方面说法指出，此次FDA拒批的原因仍与卡瑞利珠单抗的生产和质量控制(CMC)问题有关。而“双艾”组合第一次遭拒的原因也涉及CMC问题。2024年5月，恒瑞医药第一次收到该上市申请的完整回复信，FDA在回复信中表示，由于生产场地检查缺陷和部分国家的旅行限制，导致无法全部完成该项目必需的生物学研究监测计划（BIMO）临床检查，该申请无法在规定审查时间内得到批准。同年10月，恒瑞医药表示已重新向FDA提交注射用卡瑞利珠单抗联合甲磺酸阿帕替尼片肝癌一线治疗适应证上市申请并获受理。恒瑞医药表示，相关生产场地在2025年1月再次接受FDA检查，FDA核实去年发出CRL的检查中发现的问题都已经整改完毕，仅提出了3个新的改进要求，公司在规定时间内已对相关问题进行了积极回复，并一直与FDA保持密切沟通。公司将在确认具体原因后尽快采取措施并重新提交申请，以期能够获得批准。Milestone：Etripamil鼻喷雾剂3月28日，FDA 拒绝批准Milestone Pharmaceuticals的Cardamyst (etripamil) 鼻喷雾剂用于治疗阵发性室上性心动过速 (PSVT)，导致该公司股价在消息发布后下跌逾 60%。Milestone 指出，CRL主要集中在CMC问题，不涉及临床研究。在CRL中FDA要求：NDA递交后根据新指南递交亚硝胺杂质补充信息；针对NDA审评期间更换的设备开展现场检查以确保其遵循cGMP。Milestone制药称对CRL表示失望，其团队将评估反馈并计划与FDA召开A类会议以讨论CRL事项。Etripamil Nasal Spray（商品名CARDAMYST™）是Milestone Pharmaceuticals开发的一种新型钙通道阻滞剂鼻喷雾剂，用于治疗阵发性室上性心动过速（PSVT）。Aldeyra：Reproxalap4月3日，美国FDA再次驳回了Aldeyra Therapeutics在研干眼症药物Reproxalap的新药上市申请 (NDA)。Aldeyra计划在未来几周内与FDA 会面，讨论本次CRL的具体内容和后续要求。FDA明确指出，需要更多临床数据来支持该药物的有效性，要求Aldeyra至少再完成一项充分且良好对照的临床试验 ，以确保reproxalap在改善干眼症相关眼部症状方面的疗效。FDA明确的关注有包括治疗臂间基线评分差异在内的方法学相关问题对结果解释等。Reproxalap为一款活性醛化物质（RASP）抑制剂，活性醛化物质含量会在眼部或系统性发炎时上升，造成眼睛发炎、泪水分泌降低、眼睛发红以及改变泪水内脂质组成，许多干眼症患者具有较高的活性醛化物质含量。2023年11月，FDA曾对Reproxalap干眼症NDA发出的CRL，指出Reproxalap未能证明治疗干眼症的有效性，同样要求至少需要额外开展一个控制良好和充分的试验证明有效性。再生元：EYLEA HD2025年4月18日，FDA已向再生元发出了完全回复信函（CRL），拒绝了其将EYLEA HD®（阿柏西普8mg注射液）的给药间隔从最长16周延长至24周的sBLA。FDA不同意再生元关于增加额外延长给药间隔的提议，但并未提供进一步的解释。再生元表示，监管机构并未指出任何安全性或有效性问题。Regeneron正在评估FDA的决定，并将在适当的时候确定未来的行动方案。EYLEA HD被批准用于湿性年龄相关性黄斑变性（wAMD）和糖尿病性黄斑水肿（DME）患者的给药间隔为每8至16周，以及糖尿病视网膜病变（DR）患者的给药间隔为每8至12周，此前需连续3个月每月给药一次。在FDA拒绝延长给药间隔的前一天，FDA已接受了再生元关于批准Eylea HD用于治疗视网膜静脉阻塞（RVO）后黄斑水肿以及将Eylea HD在所有已批准适应症中的给药频率扩大至每四周一次的补充生物制品许可申请（sBLA）并授予优先审评资格。目前的最低给药间隔在加载期后为每八周一次， FDA的目标审批日期是2025年8月19日。Telix：Pixclara4月28日，美国FDA向Telix Pharmaceuticals发出了一封完整回应函，针对其神经胶质瘤成像剂TLX-101-CDx（18F-floretyrosine或18F-FET，Pixclara）的 NDA，指出需要额外的确认性临床证据。Telix表示有几种方法可以解决 CRL 问题，包括重新分析现有（未公开）数据，或开展额外的临床试验。Pixclara是一种PET试剂，用于表征成人和儿童患者治疗相关变化引起的进展性或复发性神经胶质瘤。FET PET已被纳入神经胶质瘤成像的国际临床实践指南中，但目前美国还没有FDA批准的用于成人和儿童脑癌成像的靶向氨基酸PET试剂，鉴于Pixclara有可能解决严重未满足的医疗需求，它已被FDA指定为孤儿药并授予快速通道指定。参考资料：各公司公告