SILVER SPRING, Md., Dec. 8, 2023 /PRNewswire/ -- Today, the U.S. Food and Drug Administration approved two milestone treatments, Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. Additionally, one of these therapies, Casgevy, is the first FDA-approved treatment to utilize a type of novel genome editing technology, signaling an innovative advancement in the field of gene therapy..

SILVER SPRING，Md.，2023年12月8日/PRNewswire/--今天，美国食品和药物管理局批准了两种里程碑式的治疗方法，即Casgevy和Lyfgenia，这是第一种用于治疗12岁及以上患者镰状细胞病（SCD）的基于细胞的基因疗法。此外，其中一种疗法Casgevy是FDA批准的第一种利用新型基因组编辑技术的疗法，标志着基因治疗领域的创新进步。。

Sickle cell disease is a group of inherited blood disorders affecting approximately 100,000 people in the U.S. It is most common in African Americans and, while less prevalent, also affects Hispanic Americans. The primary problem in sickle cell disease is a mutation in hemoglobin, a protein found in red blood cells that delivers oxygen to the body's tissues.

镰状细胞病是一组遗传性血液疾病，影响美国约10万人。它在非裔美国人中最常见，虽然不太普遍，但也影响西班牙裔美国人。镰状细胞病的主要问题是血红蛋白突变，血红蛋白是一种在红细胞中发现的蛋白质，可将氧气输送到人体组织。

This mutation causes red blood cells to develop a crescent or 'sickle' shape. These sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the body's tissues, leading to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs).

这种突变导致红细胞形成新月形或“镰刀形”。这些镰状红细胞限制血管的流动，限制氧气输送到身体组织，导致严重的疼痛和器官损伤，称为血管闭塞事件（VOEs）或血管闭塞危机（VOCs）。

The recurrence of these events or crises can lead to life-threatening disabilities and/or early death. .

这些事件或危机的复发可能导致危及生命的残疾和/或过早死亡。。

'Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,' said Nicole Verdun, M.D., director of the Office of Therapeutic Products within the FDA's Center for Biologics Evaluation and Research.

医学博士妮可·凡尔登（NicoleVerdun）说：“镰状细胞病是一种罕见的、使人衰弱且危及生命的血液疾病，其需求严重未得到满足，我们很高兴通过批准两种基于细胞的基因疗法来推进这一领域，特别是对于那些生活受到该疾病严重干扰的个体。”。，FDA生物制剂评估和研究中心治疗产品办公室主任。

'Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.' .

“基因治疗有望提供更有针对性和有效的治疗，特别是对于目前治疗选择有限的罕见疾病患者。”。

Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients' hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology..

Casgevy是一种基于细胞的基因疗法，被批准用于治疗12岁及以上复发性血管闭塞性危象患者的镰状细胞病。Casgevy是FDA批准的第一种利用CRISPR/Cas9（一种基因组编辑技术）的疗法。使用CRISPR/Cas9技术通过基因组编辑对患者的造血（血液）干细胞进行修饰。。

CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery.

CRISPR/Cas9可以被引导在目标区域切割DNA，从而能够准确编辑（删除，添加或替换）被切割的DNA。经过修饰的血液干细胞被移植回患者体内，在那里它们在骨髓内植入（附着和繁殖），并增加胎儿血红蛋白（HbF）的产生，HbF是一种促进氧气输送的血红蛋白。

In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells..

在镰状细胞病患者中，HbF水平升高可防止红细胞镰状化。。

Lyfgenia is a cell-based gene therapy. Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification and is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events. With Lyfgenia, the patient's blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease.

Lyfgenia是一种基于细胞的基因疗法。Lyfgenia使用慢病毒载体（基因传递载体）进行基因修饰，并被批准用于治疗12岁及以上患有镰状细胞病和血管闭塞事件史的患者。对于Lyfgenia，患者的血液干细胞经过基因修饰产生HbAT87Q，HbAT87Q是一种基因治疗衍生的血红蛋白，其功能类似于血红蛋白a，血红蛋白a是未受镰状细胞病影响的人产生的正常成人血红蛋白。

Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient..

含有HbAT87Q的红细胞镰刀状和阻塞血流的风险较低。然后将这些修饰的干细胞输送给患者。。

Both products are made from the patients' own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. Prior to treatment, a patients' own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia.

这两种产品都是由患者自己的造血干细胞制成的，经过修饰，作为造血（血液）干细胞移植的一部分，一次性单剂量输注给患者。在治疗之前，收集患者自己的干细胞，然后患者必须进行清髓调理（高剂量化疗），这是一种从骨髓中去除细胞的过程，以便可以用Casgevy和Lyfgenia中的修饰细胞替代。

Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product's safety and effectiveness..

接受Casgevy或Lyfgenia治疗的患者将接受长期研究，以评估每种产品的安全性和有效性。。

'These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,' said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research. 'Today's actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA's commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.'.

FDA生物制剂评估与研究中心主任、医学博士彼得·马克斯（PeterMarks）说，这些批准代表了一项重要的医学进步，它利用创新的基于细胞的基因疗法来针对潜在的毁灭性疾病并改善公众健康今天的行动是在严格评估支持批准所需的科学和临床数据之后进行的，这反映了FDA致力于促进开发安全有效的治疗方法，以应对严重影响人类健康的疾病。”。

Data Supporting Casgevy

数据支持Casgevy

The safety and effectiveness of Casgevy were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period.

Casgevy的安全性和有效性在成人和青少年SCD患者正在进行的单臂多中心试验中进行了评估。在筛查前的两年中，患者每年都有至少两种方案定义的严重挥发性有机化合物的病史。主要疗效结果是在24个月的随访期间至少连续12个月没有严重的VOC发作。

A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection..

共有44名患者接受了卡西维治疗。在有足够随访时间可评估的31例患者中，有29例（93.5%）达到了这一结果。所有接受治疗的患者均成功植入，没有患者出现移植物衰竭或移植物排斥反应。。

The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.

最常见的副作用是血小板和白细胞水平低，口腔溃疡，恶心，肌肉骨骼疼痛，腹痛，呕吐，发热性中性粒细胞减少症（发烧和白细胞计数低），头痛和瘙痒。

Data Supporting Lyfgenia

支持Lyfgenia的数据

The safety and effectiveness of Lyfgenia is based on the analysis of data from a single-arm, 24-month multicenter study in patients with sickle cell disease and history of VOEs between the ages of 12- and 50- years old. Effectiveness was evaluated based on complete resolution of VOEs (VOE-CR) between 6 and 18 months after infusion with Lyfgenia.

Lyfgenia的安全性和有效性是基于对12至50岁镰状细胞病和VOE病史患者的单臂24个月多中心研究数据的分析。在输注Lyfgenia后6至18个月之间，根据VOE（VOE-CR）的完全分辨率评估有效性。

Twenty-eight (88%) of 32 patients achieved VOE-CR during this time period. The most common side effects included stomatitis (mouth sores of the lips, mouth, and throat), low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and underlying disease..

在此期间，32名患者中有28名（88%）达到了VOE-CR。最常见的副作用包括口腔炎（嘴唇，口腔和喉咙的口疮），血小板，白细胞和红细胞水平低，以及发热性中性粒细胞减少症（发烧和白细胞计数低），与化疗和潜在疾病一致。。

Hematologic malignancy (blood cancer) has occurred in patients treated with Lyfgenia. A black box warning is included in the label for Lyfgenia with information regarding this risk. Patients receiving this product should have lifelong monitoring for these malignancies.

在接受Lyfgenia治疗的患者中发生了血液系统恶性肿瘤（血癌）。Lyfgenia的标签中包含一个黑匣子警告，其中包含有关此风险的信息。接受该产品的患者应终身监测这些恶性肿瘤。

Both the Casgevy and Lyfgenia applications received Priority Review, Orphan Drug, Fast Track and Regenerative Medicine Advanced Therapy designations.

Casgevy和Lyfgenia申请均获得优先审查，孤儿药，快速通道和再生医学高级治疗指定。

The FDA granted approval of Casgevy to Vertex Pharmaceuticals Inc. and approval of Lyfgenia to Bluebird Bio Inc.

FDA批准Vertex Pharmaceuticals Inc.使用Casgevy，批准Bluebird Bio Inc.使用Lyfgenia。

Media Contact: Carly (Kempler) Pflaum, 240-672-8872 Consumer Inquiries: Email, 888-INFO-FDA

媒体联系人：Carly（Kempler）Pflaum，240-672-8872消费者咨询：电子邮件，888-INFO-FDA

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products. .

美国食品和药物管理局（FDA）是美国卫生与公众服务部（U.S.Department of Health and Human Services）的一个机构，它通过确保人类和兽药、疫苗和其他人类使用的生物制品以及医疗器械的安全性、有效性和安全性来保护公众健康。该机构还负责我国食品供应、化妆品、膳食补充剂、辐射电子产品的安全和安保，并负责监管烟草产品。。

SOURCE U.S. Food and Drug Administration

来源：美国食品和药物管理局