新药研发不易！蓝鸟(Bluebird Bio)暂停LentiGlobin基因疗法1/2、3期临床研究

药时代编者按：

新药研发是一场充满风险的漫漫长征，

期间遇到挫折、折戟沉沙时有发生。

今天，

基因疗法研发赛道传来了

一条令人忧伤的消息。

我们在此与同药们快速分享。

请允许我们用这首歌曲表达我们忧伤的心情。

我们向勇敢的英雄们致敬！

今天，我们都是一只小小的蓝鸟，

都是一个蓝鸟人！

真心希望公司尽快查出原因，

项目继续进行！

（图片来源：蓝鸟公司官网）

美国当地时间2021年2月16日，著名的基因疗法公司蓝鸟生物（bluebird bio, Inc.）宣布，由于可疑的非预期严重不良反应急性髓细胞白血病（AML），公司已经暂停其LentiGlobin基因疗法用于镰状细胞疾病（SCD）的1/2期（HGB-206）和3期（HGB-210）临床研究。

根据HGB-206和HGB-210的临床研究方案，蓝鸟生物在上周收到关于HGB-206 A组中治疗了五年以上的患者被诊断出AML的报告后将研究暂停。公司正在调查此受试者罹患AML的原因，以确定是否与LentiGlobin基因疗法的生产中使用BB305慢病毒载体存在任何关系。另外，上周公司还收到了第二个SUSAR报告，HGB-206 C组的一名患者被检查出了骨髓增生异常综合症（MDS）。目前公司正在进行调查。

接受已上市的betibeglogene autotemcel（在欧盟和英国的商品名：ZYNTEGLO）治疗输血依赖性β-地中海贫血的患者目前没有被报道血液系统恶性肿瘤病例，但是因为它使用相同的BB305慢病毒作为载体，蓝鸟公司已决定在评估AML病例期间暂时中止ZYNTEGLO的销售。

蓝鸟CEO尼克·莱斯利（Nick Leschly）先生表示：“每一位参加我们的研究或接受我们基因疗法的患者的安全都是我们的重中之重。我们致力于与支持我们临床研究的医疗保健提供商和监管机构合作，全面评估这些病例。”

监视该公司研究的独立安全审查委员会以及美国食品药品管理局（FDA）和欧洲药品管理局（EMA）已获悉此类情况，蓝鸟生物将继续与监管机构合作完成调查。

了解详情，请阅读公司新闻稿。谢谢！

bluebird bio Announces Temporary Suspension on Phase 1/2 and Phase 3 Studies of LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111)

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 16, 2021-- bluebird bio, Inc. (Nasdaq: BLUE) announced today that the company has placed its Phase 1/2 (HGB-206) and Phase 3 (HGB-210) studies of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) on a temporary suspension due to a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML).

In line with the clinical study protocols for HGB-206 and HGB-210, bluebird bio placed the studies on temporary suspension following a report received last week that a patient who was treated more than five years ago in Group A of HGB-206 was diagnosed with AML. The company is investigating the cause of this patient’s AML in order to determine if there is any relationship to the use of BB305 lentiviral vector in the manufacture of LentiGlobin gene therapy for SCD. In addition, a second SUSAR of myelodysplastic syndrome (MDS) in a patient from Group C of HGB-206 was reported last week to the company and is currently being investigated.

No cases of hematologic malignancy have been reported in any patient who has received treatment with betibeglogene autotemcel for transfusion-dependent β-thalassemia (licensed as ZYNTEGLO in the European Union and the United Kingdom), however because it is also manufactured using the same BB305 lentiviral vector used in LentiGlobin gene therapy for SCD, the company has decided to temporarily suspend marketing of ZYNTEGLO while the AML case is assessed.

“The safety of every patient who has participated in our studies or is treated with our gene therapies is the utmost priority for us,” said Nick Leschly, chief bluebird. “We are committed to fully assessing these cases in partnership with the healthcare providers supporting our clinical studies and appropriate regulatory agencies. Our thoughts are with these patients and their families during this time.”

The independent safety review board monitoring the company’s studies as well as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have been advised of these cases and bluebird bio will continue to work with regulatory agencies to complete its investigation.

Investor Conference Call Information

bluebird bio will hold a conference call to discuss this update on Tuesday, February 16 at 8:00 a.m. ET. Investors may listen to the call by dialing [phone] from locations in the United States or [phone] from outside the United States. Please refer to conference ID number 880-6406.

To access the live webcast of bluebird bio’s presentation, please visit the “Events & Presentations” page within the Investors & Media section of the bluebird bio website at http://investor.bluebirdbio.com. A replay of the webcast will be available on the bluebird bio website for 90 days following the event.

About HGB-206 and HGB-210

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A, B and C. A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

HGB-210 is an ongoing Phase 3 single-arm open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for SCD in patients between two years and 50 years of age with sickle cell disease.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About ZYNTEGLO (betibeglogene autotemcel)

Betibeglogene autotemcel (beti-cel) is a one-time gene therapy that adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived adult Hb, at levels that may eliminate or significantly reduce the need for transfusions. In studies of beti-cel, transfusion independence (TI) is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

The European Commission granted conditional marketing authorization (CMA) for beti-cel, marketed as ZYNTEGLO™ gene therapy, for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

For details, please see the Summary of Product Characteristics (SmPC).

On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for beti-cel. The CMA for beti-cel is valid in the 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway.

The U.S. Food and Drug Administration granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the U.S. Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study, LTF-303 for people who have participated in bluebird bio-sponsored clinical studies of ZYNTEGLO.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

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