The purpose of the study is to evaluate the efficacy and safety of CTX001 (exa-cel) in adolescent and adult participants with severe sickle cell disease (SCD), βS/βC genotype (HbSC).

开始日期2024-04-01

申办/合作机构

Vertex Pharmaceuticals, Inc.

ChiCTR2300073795 / Recruiting早期临床1期IIT

An International, Multicenter, Phase I Open Label Study to Evaluate Safety and Efficacy of Administration of Autologous CD34+ Cells Gene Edited Ex Vivo Using a CRISPR/AAV6 Platform to Introduce a Codon Optimized cDNA Version of the Red-Cell Type Pyruvate Kinase Genein Adult and Pediatric Patients with Severe Pyruvate Kinase

开始日期2023-11-09

申办/合作机构

上海儿童医学中心

CTIS2024-514641-12-00 / Recruiting

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects with Transfusion-Dependent ß-Thalassemia or Severe Sickle Cell Disease - VX21-CTX001-161

开始日期2023-06-07

申办/合作机构

Vertex Pharmaceuticals, Inc.

100 项与 Exagamglogene Autotemcel 相关的临床结果

登录后查看更多信息

100 项与 Exagamglogene Autotemcel 相关的转化医学

登录后查看更多信息

100 项与 Exagamglogene Autotemcel 相关的专利（医药）

登录后查看更多信息

项与 Exagamglogene Autotemcel 相关的文献（医药）

2024-07-01·Journal of Genetics and Genomics

Gene therapy and gene editing strategies in inherited blood disorders

Review

作者: Song, Xuemei ; Zheng, Tingfeng ; Guo, Xiang ; Wang, Xiaolong ; Liu, JinLei ; Chen, Tangcong

Gene therapy has shown significant potential in treating various diseases, particularly inherited blood disorders such as hemophilia, sickle cell disease, and thalassemia. Advances in understanding the regulatory network of disease-associated genes have led to the identification of additional therapeutic targets for treatment, especially for β-hemoglobinopathies. Erythroid regulatory factor BCL11A offers the most promising therapeutic target for β-hemoglobinopathies and reduction of its expression using the commercialized gene therapy product Casgevy was approved for use in the UK and USA in 2023. Notably, the emergence of innovative gene editing technologies has further broadened the gene therapy landscape, presenting new possibilities for treatment. Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future.

2024-05-09·The New England journal of medicine

Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia

Article

作者: Simard, Christopher ; Mapara, Markus ; Lang, Peter ; Ross, Leorah ; Kattamis, Antonis ; Liem, Robert I ; Wall, Donna ; Corbacioglu, Selim ; Frangoul, Haydar ; Algeri, Mattia ; Kohli, Puja ; Carpenter, Ben ; Shi, Daoyuan ; Shah, Ami J ; Zhang, Lanju ; Li, Amanda M ; Cappellini, Maria Domenica ; de la Fuente, Josu ; Morrow, Phuong Khanh ; Sheth, Sujit ; Locatelli, Franco ; Kwiatkowski, Janet L ; Grupp, Stephan ; Hobbs, William E ; Bobruff, Yael ; Handgretinger, Rupert ; Meisel, Roland

BACKGROUND:

Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing of the erythroid-specific enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).

METHODS:

We conducted an open-label, single-group, phase 3 study of exa-cel in patients 12 to 35 years of age with transfusion-dependent β-thalassemia and a β⁰/β⁰, β⁰/β⁰-like, or non-β⁰/β⁰-like genotype. CD34+ HSPCs were edited by means of CRISPR-Cas9 with a guide mRNA. Before the exa-cel infusion, patients underwent myeloablative conditioning with pharmacokinetically dose-adjusted busulfan. The primary end point was transfusion independence, defined as a weighted average hemoglobin level of 9 g per deciliter or higher without red-cell transfusion for at least 12 consecutive months. Total and fetal hemoglobin concentrations and safety were also assessed.

RESULTS:

A total of 52 patients with transfusion-dependent β-thalassemia received exa-cel and were included in this prespecified interim analysis; the median follow-up was 20.4 months (range, 2.1 to 48.1). Neutrophils and platelets engrafted in each patient. Among the 35 patients with sufficient follow-up data for evaluation, transfusion independence occurred in 32 (91%; 95% confidence interval, 77 to 98; P<0.001 against the null hypothesis of a 50% response). During transfusion independence, the mean total hemoglobin level was 13.1 g per deciliter and the mean fetal hemoglobin level was 11.9 g per deciliter, and fetal hemoglobin had a pancellular distribution (≥94% of red cells). The safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous HSPC transplantation. No deaths or cancers occurred.

CONCLUSIONS:

Treatment with exa-cel, preceded by myeloablation, resulted in transfusion independence in 91% of patients with transfusion-dependent β-thalassemia. (Supported by Vertex Pharmaceuticals and CRISPR Therapeutics; CLIMB THAL-111 ClinicalTrials.gov number, NCT03655678.).

2024-05-09·The New England journal of medicine

Exagamglogene Autotemcel for Severe Sickle Cell Disease

Article

作者: Simard, Christopher ; Cavazzana, Marina ; Liem, Robert I ; Eckrich, Michael J ; Zhou, Weiyu ; Xuan, Fengjuan ; Wall, Donna ; de Montalembert, Mariane ; Shah, Ami J ; Lobitz, Stephan ; Walters, Mark C ; Molinari, Lyndsay ; Dedeken, Laurence ; Steinberg, Martin H ; Morrow, Phuong Khanh ; Sharma, Akshay ; Meisel, Roland ; Bower, Laura ; Rondelli, Damiano ; Locatelli, Franco ; Frangoul, Haydar ; Corbacioglu, Selim ; Grupp, Stephan A ; Hobbs, William E ; Bhatia, Monica ; Telfer, Paul ; Mapara, Markus ; Imren, Suzan

BACKGROUND:

Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis by means of ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at the erythroid-specific enhancer region of BCL11A.

METHODS:

We conducted a phase 3, single-group, open-label study of exa-cel in patients 12 to 35 years of age with sickle cell disease who had had at least two severe vaso-occlusive crises in each of the 2 years before screening. CD34+ HSPCs were edited with the use of CRISPR-Cas9. Before the exa-cel infusion, patients underwent myeloablative conditioning with pharmacokinetically dose-adjusted busulfan. The primary end point was freedom from severe vaso-occlusive crises for at least 12 consecutive months. A key secondary end point was freedom from inpatient hospitalization for severe vaso-occlusive crises for at least 12 consecutive months. The safety of exa-cel was also assessed.

RESULTS:

A total of 44 patients received exa-cel, and the median follow-up was 19.3 months (range, 0.8 to 48.1). Neutrophils and platelets engrafted in each patient. Of the 30 patients who had sufficient follow-up to be evaluated, 29 (97%; 95% confidence interval [CI], 83 to 100) were free from vaso-occlusive crises for at least 12 consecutive months, and all 30 (100%; 95% CI, 88 to 100) were free from hospitalizations for vaso-occlusive crises for at least 12 consecutive months (P<0.001 for both comparisons against the null hypothesis of a 50% response). The safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous HSPC transplantation. No cancers occurred.

CONCLUSIONS:

Treatment with exa-cel eliminated vaso-occlusive crises in 97% of patients with sickle cell disease for a period of 12 months or more. (CLIMB SCD-121; ClinicalTrials.gov number, NCT03745287.).

602

项与 Exagamglogene Autotemcel 相关的新闻（医药）

2024-09-19

·GlobeNewswire-Health Care

Disc Medicine Expands Leadership Team with Appointment of Industry Veteran Steve Caffé, MD as Chief Regulatory Officer

Dr. Steve Caffé is an accomplished industry executive with over 25 years of expertise in global product development and regulatory affairsWATERTOWN, Mass., Sept. 19, 2024 (GLOBE NEWSWIRE) -- Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, today announced the appointment of Steve Caffé, MD as the company’s Chief Regulatory Officer. Dr. Caffé is an experienced biotech executive with significant expertise in global regulatory leadership across a wide range of therapeutic areas, including hematology, oncology, and rare diseases. “We are excited to welcome an executive as accomplished as Steve to Disc, where his depth of regulatory expertise and experience in global product development will be integral to the company’s growth,” said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc. “Steve’s track record of successful drug approvals across multiple disease areas and geographies will be a significant advantage for Disc as we move into the later stages of development across our portfolio.” “I am excited to be joining Disc at this pivotal moment in the company’s transition to a late-stage hematology company,” said Dr. Caffé. “With significant trial initiations coming in the next year for all three pipeline programs, I look forward to leading global regulatory interactions to support Disc’s mission of delivering novel treatments to patients with high unmet need. I am excited to work with the talented team at Disc and build on the excellent work done to date.” Dr. Caffé has more than 25 years of experience in global product development and regulatory affairs, having held senior leadership positions at several top biotechnology companies. Most recently, he served as Head of Regulatory Affairs at CRISPR Therapeutics where he was involved in the development and approval of Casgevy® (exagamglogene autotemcel) for sickle cell disease and beta thalassemia. Prior to joining CRISPR, Dr Caffé was the Senior Vice President leading Regulatory Affairs, Pharmacovigilance, Quality, and Patient Advocacy at Ra Pharmaceuticals. Before this, Dr. Caffé held senior-level regulatory positions at a number of other biopharmaceutical companies, including Sucampo Pharmaceuticals, AMAG Pharmaceuticals, MedImmune (Biologics Division of AstraZeneca), Baxter, Sanofi-Aventis and Merck. Across these experiences, Dr. Caffé has contributed to over 40 new drug approvals and major new indications worldwide in a wide range of therapeutic areas. Steve received his M.D. at the Université Pierre et Marie Curie in Paris, France. In connection with Dr. Caffé’s appointment, on September 16, 2024, Disc granted to Dr. Caffé an inducement equity award outside of Disc’s Amended and Restated 2021 Stock Option and Incentive Plan in accordance with Nasdaq Listing Rule 5635(c)(4), comprised of (i) an option to purchase 55,000 shares (the “Option Award”) of Disc’s common stock (“Common Stock”), at an exercise price equal to the closing price of the Common Stock on the date of grant, and (ii) a restricted stock unit award for 36,666 shares of Common Stock (the “RSU Award” and, together with the Option Award, the “Inducement Award”). The Option Award shall vest 25% on September 16, 2025, with the remainder vesting in 36 equal monthly installments thereafter. The RSU Award shall vest in equal installments on each of the first, second, third, and fourth anniversaries of the vesting date set by Disc’s company vesting policy. The Inducement Award was approved by the Compensation Committee of Disc’s Board of Directors. About Disc Medicine Disc Medicine (NASDAQ:IRON) is a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel treatments for patients who suffer from serious hematologic diseases. We are building a portfolio of innovative, potentially first-in-class therapeutic candidates that aim to address a wide spectrum of hematologic diseases by targeting fundamental biological pathways of red blood cell biology, specifically heme biosynthesis and iron homeostasis. For more information, please visit www.discmedicine.com. Disc Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding Disc’s expectations with respect to the chief regulatory officer position, upcoming trial initiations in the next year, and Disc’s clinical development plans and related regulatory interactions. The use of words such as, but not limited to, “believe,” “expect,” “estimate,” “project,” “intend,” “future,” “potential,” “look forward,” “continue,” “may,” “might,” “plan,” “will,” “should,” “seek,” “anticipate,” or “could” or the negative of these terms and other similar words or expressions that are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Disc’s current beliefs, expectations and assumptions regarding the future of Disc’s business, future plans and strategies, clinical results and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Disc may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and investors should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements as a result of a number of material risks and uncertainties including but not limited to: Disc’s expectations regarding the chief regulatory officer position; Disc’s expectations regarding leadership and future growth; Disc’s expectations regarding its research and development programs; Disc’s expectations of entering late-stage development; and the other risks and uncertainties described in Disc’s filings with the Securities and Exchange Commission, including in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2023, and in subsequent Quarterly Reports on Form 10-Q. Any forward-looking statement speaks only as of the date on which it was made. None of Disc, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. Media Contact Peg RusconiDeerfield Grouppeg.rusconi@deerfieldgroup.com Investor Relations Contact Christina TartagliaPrecision AQchristina.tartaglia@precisionaq.com

高管变更

2024-09-17

·BioSpace

Patients At Last Begin Receiving Vertex-CRISPR and Bluebird Sickle Cell Gene Therapies

iStock/ lukutin77 Last month, Vertex said sickle cell patients had not yet received infusions of its gene therapy Casgevy. That’s now changed, as the company races with bluebird bio’s Lyfgenia. As of second-quarter earnings on August 1, no patients had received an infusion of Vertex Pharmaceuticals and CRISPR Therapeutics’ sickle cell gene therapy Casgevy. But infusions have since begun, a spokesperson for Vertex confirmed to BioSpace . Meanwhile, over at peer company bluebird bio, which earned FDA approval of its sickle cell gene therapy Lyfgenia the same day as Casgevy , patients are also beginning to receive infusions of their own edited cells, The New York Times reported on Monday. These moments mark a breakthrough for sickle cell treatment. Experts expected the uptake of gene therapies to be slow as the process to undergo treatment can take as long as a year. Vertex’s Chief Operating Officer Stuart Arbuckle acknowledged as much in the earnings call last month. “We have always known that Casgevy offers an enormous advancement for patients. We’ve also consistently communicated that the patient journey, that is the process to go from patient interest all the way to infusion of edited cells, is long and complex. Whilst it’s still early in the launch, we have gained many learnings. Interest level is high among patients, physicians, governments and other stakeholders,” Arbuckle said. Vertex did not respond to requests for more information as of publication, including on the number of patients receiving Casgevy. As for bluebird, which was expected to have a faster rollout of Lyfgenia because it already had treatment centers established for its two other FDA-approved gene therapies, the company announced during a second quarter earnings call on August 14 that four patients had undergone cell collection as a first step to Lyfgenia treatment. When Will Casgevy and Lyfgenia Start Generating Revenue? At the time of its Q2 earnings call, Vertex had activated 35 centers with a goal of activating 75 around the world. About 20 patients had offered up their cells for collection, putting them “in the funnel” for treatment. Vertex was not specific, but said the patients were coming from all regions where the medicine is approved, which includes the U.S., Europe and the Middle East. Arbuckle noted on the call that the company has also been working to improve reimbursement in all jurisdictions to ensure patients have coverage. “The treatment process does take time, but we are now even more confident in our view that Casgevy will help large numbers of patients around the world and represents a multibillion-dollar opportunity,” Arbuckle said. Investors have been eager to know when Casgevy treatments will begin, with analysts peppering executives with questions on the earnings call to try and get any scrap of information. William Blair has estimated that peak sales for the gene therapy could reach $3.6 billion, even with the slow start. As for Lyfgenia, bluebird bio CFO James Sterling said on the call that investors can expect about two quarters between initial cell collection and revenue recognition. “We are clearly on the right track with accelerating interest in our therapies, and a clear path to translate patient starts into a growing consistent revenue stream over time.” Sterling noted that patients are scheduling their treatment out many months in advance, often around life events given the time commitment to undergoing gene therapy. “So it’s not a slower start than expected and it’s not a demand issue. Demand is actually strong. It’s simply a timing issue,” he said.

基因疗法

2024-09-11

·CPHI制药在线

从2100万到3000万一针，盘点全球最昂贵五大药物市场逻辑

关注并星标CPHI制药在线随着行业对于罕见病领域的不断关注以及投入，近几年罕见病药物也不断迎来重大突破，在过去四五年的时间里，美国FDA批准的孤儿药数量（美国《孤儿药法案》将罕见病定义为在美国影响不到 20 万人的任何疾病或病症）已经占到了创新药批准总数的一半以上，在这背后离不开以FDA为代表的药监机构的审评支持，更离不开产业界对于罕见病药物的不断投入。图1：FDA2010年-2023年批准的孤儿药占创新药批准比例（FDA官方数据）但终究罕见病药物开发公司需要在药物的商业推广中寻求平衡和利润，由于罕见病领域患者实属有限，在一定程度上也直接导致了近几年一款又一款天价药物的诞生。在今年上半年，Orchard Therapeutics的早发性异染性脑白质营养不良（MLD）一次性基因疗法Lenmeldy获FDA批准上市，定价425万美元，一举成为了全球当前最昂贵的药物。尽管Lenmeldy的批准为MLD的患者带来了曙光，但其如此高昂的定价相信一定会让患者望而却步，而在一款又一款天价药物的诞生的背后，不仅是让患者以及支付体系望而却步，也让开发公司的商业化举步维艰，这一切也都反映出了所有行业参与者的无奈。 01 盘点全球最昂贵的五款药物 No.1 Lenmeldy--425万美元/剂 Lenmeldy (atidarsagene autotemcel)是一款基因疗法药物，由Orchard Therapeutics开发，2024年获得FDA批准用于治疗早发性异染性脑白质营养不良（MLD）。MLD是一种影响大脑和神经系统的使人衰弱的罕见遗传疾病。是由一种名为芳基硫酸酯酶a（ARSA）的酶缺乏引起的，导致细胞中硫酸盐（脂肪物质）的蓄积。这种蓄积会对中枢和外周神经系统造成损害，表现为运动和认知功能的丧失甚至早亡。据估计在美国每40000人中就有一人患有MLD。MLD没有治愈方法，治疗通常侧重于支持性护理和症状管理。 Lenmeldy是一种一次性、个性化单剂量输注，由患者自身造血干细胞（HSC）制成，这些干细胞经过基因修饰，包括ARSA基因的功能拷贝。从患者身上收集干细胞，并通过添加ARSA基因的功能拷贝进行修饰。经过修饰的干细胞被输回患者体内，在骨髓中植入（附着和繁殖）。经过修饰的干细胞为身体提供产生ARSA酶的骨髓（免疫）细胞，ARSA酶有助于分解有害的硫酸盐蓄积，并可能阻止MLD的进展。在治疗之前，患者必须接受高剂量化疗，去除骨髓中细胞，以便用Lenmeldy中的修饰细胞替换。在欧洲Lenmeldy的定价策略略低于美国，数据显示其德国为定价约为240万美金/剂，英国则为310万美金。到目前为止，Lenmeldy 已在意大利、丹麦、德国、英国、法国、挪威和荷兰等国家获得了市场准入，但销售额仅仅只有1270万美金，这意味着只有极少数患者获得了治疗。尽管如此，GlobalData还是预计这款药物在2029年可以达到1亿美金的收入。 No.2 Hemgenix--350万美金/剂；Beqvez--350万美金/剂在Lenmeldy获批之前，同为基因疗法的Hemgenix是全球价格最高的药物。2022年11月22日，CSL Behring和unique的B型血友病基因疗法Hemgenix（etranacogene dezaparvovec）获FDA批准上市，成为首个获批治疗这种罕见疾病的基因疗法。据悉，该药每剂的价格高达350万美元，是彼时全球最昂贵的药物。血友病B（hemophilia B，HB）是一种X染色体连锁的隐性遗传性出血性疾病，由凝血因子Ⅸ基因突变导致凝血因子Ⅸ（FⅨ）缺乏的一种疾病。 Beqvez由辉瑞开发在今年4月获得FDA批准，同样也是一款用于治疗B型血友病基因疗法，而作为第二款获批用于此适应症的基因疗法，Beqvez的定价同样也是350万美金/剂。根据报道，Hemgenix在截止至2023年6月的全年中，收入接近12亿美元；在2023年7-12月的半年中，销售额约为6.62亿美元。根据CSL的2024H2半年报，患者和群体对于Hemgenix的兴趣正在增加。Beqvez作为后来者，价格上Beqvez与Hemgenix持平（均为350万美元），Beqvez有希望在辉瑞的加持下交出不错的商业化成绩。一般来说，血友病基因疗法的成本及其为患者和社会提供的价值一直受到严格审查，特别是从传统疗法过渡到新的基因疗法时更是如此。但根据临床与经济审查研究所（ICER）的报告，在评估了 Hemgenix 等血友病基因疗法与因子 IX 和 VIII 预防疗法相比的临床疗效和价值后，ICER认为它们具有成本效益。 No.3 Elevidys--320万美金和上述三款药物一样的是，Elevidys同样也是一款基因疗法。2023年6月，Sarepta Therapeutics公司宣布FDA加速批准基因疗法Elevidys上市，这是一种基于腺相关病毒的基因疗法，用于治疗4至5岁杜氏肌营养不良症(duchenne muscular dystrophy, DMD)儿童患者。Elevidys是一种基因替代疗法，通过将正常的基因输注到患者体内，帮助患者持续产生具有抗肌萎缩蛋白功能的重组蛋白，这不仅是目前首款及唯一一款DMD基因疗法，也是首个通过加速批准上市的体内基因疗法，今年6月Elevidys也获得了FDA的完全批准。 DMD病理过程中的关键蛋白--抗肌萎缩蛋白的编码基因尺寸巨大，这对基因疗法的递送提出了技术挑战。Elevidys所表达的微抗肌萎缩蛋白是一种缩短的功能性抗肌萎缩蛋白，克服了因载体载荷有限所造成的限制，并且能够在肌肉中引起转基因的强力表达。这种疗法使用了从非人灵长类动物中分离出的AAVrh74病毒载体进行递送，不会穿过血脑屏障进入中枢神经系统。在前期临床推进并不是一帆风顺的情况下，Elevidys还是交出了不俗的商业化答卷，自2023年6月推出以来销售额超2亿美元，在2024 H1销售额达到了2.56亿美元，未来有希望突破十亿美元大关。 No.4 Lyfgenia--310万美金/剂 2023年12月8日，蓝鸟生物（bluebird）开发的细胞基因疗法Lyfgenia获FDA批准上市，用于治疗 12 岁及以上患有复发性血管闭塞危象 (VOC) 的镰状细胞病 (SCD) 患者，定价也是高昂的310万美金。Lyfgenia同样也是一款基于慢病毒载体的细胞基因疗法，通过慢病毒载体将功能性β珠蛋白基因永久添加到患者自身的造血干细胞（HSC）中，可持久产生具有抗镰状细胞特性的血红蛋白（HbAT87Q型），HbAT87Q型与野生型 HbA 具有相似的氧结合能力，限制红细胞镰状化，并有可能减少血管闭塞事件（VOE），这是一种一次性疗法，适用于12岁及以上的患者。在蓝鸟生物公布的一项为期24个月、涉及12至50岁镰刀型细胞贫血病和VOE病史患者的单臂多中心研究中，表明Lyfgenia的安全性与有效性良好，该临床研究对Lyfgenia输注后6至18个月内实现VOE完全消退（VOE-CR）的患者进行了跟踪研究，结果显示，在研究的32例患者中，30位患者（94%）的VOE得到有效治疗，其中的28位（88%）成功达到了VOE-CR，这其中包括了8例青少年患者。但令人遗憾的是，在蓝鸟生物公司运营举步维艰的同时，Lyfgenia的商业化表现也是一言难尽。在获得FDA批准半年之后，Lyfgenia才终于迎来自己在美国治疗的第一例患者，受此消息影响，蓝鸟的股价当日上涨11.14%，回升至1美元/股，勉强止住了之前跌落至1美元以下的颓势，Lyfgenia的未来无疑也蒙上了一层阴影。 No.5 Skysona--300万美金/剂 Skysona同样由蓝鸟生物开发，其是一款造血干细胞慢病毒体外基因疗法，于2021年7月在欧洲获批上市，但上市不到三个月，蓝鸟生物就宣布因商业策略原因退出欧洲市场。2022年9月，该药获FDA批准在美国上市用于治疗年龄在18岁以下、携带ABCD1基因突变、早期脑肾上腺脑白质营养不良（CALD）患者。 CALD是一类严重的遗传性神经疾病。它虽然罕见，但病情极为凶险，甚至能威胁到生命。据估计，每21000个男婴中，就有一名罹患肾上腺脑白质营养不良（ALD），而大约40%的患者会出现脑内进展，即CALD。但CALD在美国也极为罕见，每年只有约50人患病，蓝鸟生物预计Skysona每年治疗约10名患者，自然也很难指望其有不错的商业化表现。 02 昂贵价格背后图2：全球十大昂贵药物排名（参考自GlobalData数据库）上文中已经盘点了目前全球最为昂贵的五款药物，根据GlobalData数据库记录，目前排在全球十大昂贵药物6-10名的药物分别为Roctavian（290万）、 Rethymic（281万）、 Zynteglo （280万）、Zolgensma （232万）以及 Casgevy（220万），从这些全球最贵药物的治疗领域来看，多集中于罕见病领域，基因疗法带来了一次性治愈的可能，为患病群体带来了更多希望。摆在面前的问题也是显而易见的，昂贵几乎已成为基因疗法的代名词，让人望而却步的高昂价格几乎将绝大多数患者挡在门外，而能最终成功商业化的罕见病药物自然也是屈指可数。一些罕见病疗法曾退出区域市场，甚至全球退市，涉及基因疗法Glybera、Zynteglo、Skysona、酶替代疗法唯铭赞等。患者群体小、市场小、药物研发难度高且研发成本高，是药企研发罕见病药物热情不高、罕见病药物定价高昂的主要原因。在全球药价最高的美国市场，对罕用药保障表现为立法先行，市场激励，政府出台法律法规，联动市场参与罕用药的保障，"两只手"联合建立了世界上罕用药上市品类最多的美国模式，美国市场自然也造就了一批罕见病药物的优异的商业化表现如Alnylam或者Sarepta都已经踏上或即将踏上10亿美元收入的里程碑，罗氏，渤健和诺华的脊髓性肌萎缩症（SMA）药物累计创造了超过30亿美元的销售记录等。和美国相比，我国的的支付体系和药品经济学差异较大，在医保作为最大支付方的我国药物市场，如此高昂的罕见病药物价格也直接给医保支付带来了巨大的压力。目前，多方共付分担机制在一些地方开始出现，多方主要指包括基本医保、商业保险、社会慈善、患者自付和企业分担等在内的多种保障渠道，目前来看已经初有成效。尽管同发达国家相比，中国在罕见病药物的支付标准上仍存在一定差距，但这一差距会随着医保政策的完善和支付能力的提升而逐渐缩小。参考资料： 1. https://www.pharmaceutical-technology.com/analyst-comment/lenmeldy-becomes-worlds-most-expensive-drug/?cf-view&cf-closed； 2. https://www.biopharmadive.com/news/pfizer-fda-approval-beqvez-hemophilia-b-gene-therapy/714423/； 3. https://www.pharmaceutical-technology.com/features/the-most-expensive-drugs-in-the-us/?cf-view&cf-click&cf-minimized&cf-view&cf-click&cf-minimized&cf-view&cf-closed； 4. https://www.biopharmadive.com/news/bluebird-lyfgenia-first-cell-collection-sickle-cell/715252/； 5. 典型国家和地区罕见病用药保障模式比较及启示，李乐乐何晓彤陈湘妤李怡璇（中国人民大学劳动人事学院北京 100872）； 6. 保罕见还是保基本？"孤儿药"支付保障还需多开赛道，中国卫生杂志； 7. 罕见病用药保障现状与挑战，《罕见病研究》 2024, 3 ( 2): 155? 163 END 【智药研习社直播预告】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~

基因疗法孤儿药

100 项与 Exagamglogene Autotemcel 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15572

研发状态

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
β地中海贫血	欧盟	Vertex Pharmaceuticals, Inc.	2024-02-09
β地中海贫血	冰岛	Vertex Pharmaceuticals, Inc.	2024-02-09
β地中海贫血	列支敦士登	Vertex Pharmaceuticals, Inc.	2024-02-09
β地中海贫血	挪威	Vertex Pharmaceuticals, Inc.	2024-02-09
输血依赖性地中海贫血	美国	Vertex Pharmaceuticals, Inc.	2024-01-31
镰状细胞血症	英国	Vertex Pharmaceuticals (Europe) Ltd. (Ireland)	2023-11-15
输血依赖性β地中海贫血	英国	Vertex Pharmaceuticals (Europe) Ltd. (Ireland)	2023-11-15

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


NEWS 人工标引	N/A	输血依赖性β地中海贫血 \| 镰状细胞血症	-	Casgevy (SCD)	衊壓選夢選鏇艱構鹹廠(鑰網齋簾膚鹹鏇鏇觸遞) = 簾衊齋衊廠淵膚築繭網構築齋願鏇膚顧廠醖獵 (艱繭鏇顧願製襯衊構鹽 ) 更多	积极	2024-06-15
NEWS 人工标引	N/A	输血依赖性β地中海贫血 \| 镰状细胞血症	-	Casgevy (TDT)	簾鬱壓製積糧醖繭蓋壓(窪醖鹹顧製蓋繭簾網觸) = 廠廠選齋醖醖艱餘艱願積糧醖願鑰鬱願繭築廠 (積窪顧醖鹹範鑰餘繭糧 ) 更多	积极	2024-06-15
NCT03745287 (CLIMB SCD-121, EHA2024) 人工标引	临床3期	镰状细胞血症	46	Exagamglogene autotemcel	簾積鏇衊憲鏇鏇選艱範(簾壓選顧積鹹窪鏇鏇觸) = 範選膚鏇淵糧鬱壓艱繭衊觸遞膚築製齋醖膚簾 (鹹鹽獵鏇製廠鹹醖構襯, 79 ~ 99) 更多	积极	2024-05-14
NCT03655678 (CTX001-111 \| CLIMB THAL-111, EHA2024) 人工标引	临床3期	输血依赖性地中海贫血	24	Exagamglogene autotemcel	廠積襯衊淵衊憲顧製膚(獵壓選鹽積網選範選鬱) = 淵糧範壓簾繭網選積糧艱網鏇膚鬱遞窪壓鹹窪 (醖鑰遞鏇鬱願艱廠網積, 0.21) 更多	积极	2024-05-14
NCT03745287 (CLIMB SCD-121, EHA2024) 人工标引	临床3期	镰状细胞血症	24	exa-cel	鏇糧廠夢願選鬱鹹醖顧(獵襯遞鬱餘鏇願構壓鑰) = By month 6, EQ-5D-5L health utility US index score and EQ VAS score showed substantial improvements,which were maintained through month 24 (change at month 24 [n=17]: 0.13 [0.19]; minimal clinically important difference [MCID] 0.078 and 26.9 [22.6]; MCID 7 to 10, respectively). 遞網齋網鑰膚壓餘憲艱 (鏇膚餘繭構糧網鏇醖築 ) 更多	积极	2024-05-14
NCT03655678 (CTX001-111, FDA) 人工标引	临床2/3期	输血依赖性β地中海贫血	52	CASGEVY	鑰遞顧夢獵鏇壓遞簾襯(選構構壓鑰簾製醖壓廠) = 構選繭餘選淵襯齋築鑰觸窪壓醖選鬱鹽製餘顧 (構衊廠獵襯鏇壓艱廠鬱, 75.7 ~ 100) 更多	积极	2024-02-07
NCT03655678 (CLIMB THAL-111, Tandem Meetings ASTCT and CIBMTR2024) 人工标引	临床3期	输血依赖性β地中海贫血	44	Exagamglogene autotemcel	壓衊廠鬱鏇艱餘願齋遞(獵醖壓餘選觸積遞艱糧) = 衊淵艱鹹觸築築窪醖憲願鹹蓋蓋觸積憲製鏇願 (鏇範壓衊鑰顧獵鏇鏇獵 )	积极	2024-02-01
CLIMB THAL-111 (ASH2023)	临床3期	输血依赖性β地中海贫血	52	Exagamglogene autotemcel	簾築網艱鬱膚蓋鬱遞餘(餘獵獵網齋獵糧齋顧鏇) = 鹹齋齋襯築願觸壓範夢願鹹糧鏇願衊窪願廠餘 (鏇蓋鏇獵獵繭顧衊衊壓 ) 更多	积极	2023-12-11
CLIMB SCD-121 (ASH2023)	临床3期	镰状细胞血症	42	Exagamglogene autotemcel	鹹齋糧憲窪壓衊鹹簾淵(繭憲壓獵襯鑰壓遞獵餘) = 積範繭膚鑰製製範構夢選獵鬱獵醖醖壓選糧壓 (構糧築夢憲獵積觸淵壓, 75.1% ~ 99.9%) 更多	积极	2023-12-11
CLIMB TDT-111 (ASH2023)	临床3期	输血依赖性β地中海贫血	35	Exagamglogene autotemcel	築觸築獵壓鏇憲襯淵廠(鏇醖築蓋襯壓鑰獵膚觸) = 製鑰網製遞膚齋鏇鏇壓衊網夢網鹽製鏇鬱衊憲 (遞遞醖鏇壓觸鹽鑰簾簾 ) 更多	-	2023-12-11
NCT03745287 (FDA) 人工标引	临床2/3期	镰状细胞血症	44	CASGEVY	顧窪製糧鹽製鹽壓鬱積(齋願襯構網範獵鹽衊積) = 願窪艱觸積簾憲積廠壓憲鹽壓製壓壓積淵選憲 (鏇鏇鏇夢願選積壓鏇構, 77.9 ~ 100.0) 更多	积极	2023-12-08