A Phase 3 Study of Lenti-D Drug Product After Myeloablative Conditioning Using Busulfan and Fludarabine in Subjects ≤17 Years of Age With Cerebral Adrenoleukodystrophy (CALD)

The purpose of this study is to evaluate the efficacy and safety of Lenti-D Drug Product (also known as elivaldogene autotemcel or Skysona, hereafter referred to as eli-cel) after myeloablative conditioning with busulfan and fludarabine in participants with CALD. A participant's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the participant following myeloablative conditioning. Enrollment and treatment in Study ALD-104 have been completed and further enrollment in this study is not expected, although participants follow-up remains ongoing in the long-term follow-up Study LTF-304 (NCT02698579).

开始日期2019-01-24

申办/合作机构

bluebird bio, Inc.

NCT01896102

/ Completed临床2/3期

A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

This trial assessed the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector (also called elivaldogene autotemcel or eli-cel), for the treatment of cerebral adrenoleukodystrophy (CALD). A participant's blood stem cells were collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells were transplanted back into the participant following myeloablative conditioning. Participants in this study will be continuously followed in study LTF-304.

开始日期2013-08-21

申办/合作机构

bluebird bio, Inc.

100 项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的临床结果

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100 项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的转化医学

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100 项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的专利（医药）

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项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的文献（医药）

2024-11-01·HUMAN GENE THERAPY

Blood Cancers Reported in Seven Children Dosed with SKYSONA™

Article

作者: Philippidis, Alex

2024-10-10·NEW ENGLAND JOURNAL OF MEDICINE

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

Article

作者: Musolino, Patricia L ; Sevin, Caroline ; De Oliveira, Satiro ; McNeil, Elizabeth ; Kühl, Jörn-Sven ; Platzbecker, Uwe ; Sankar, Raman ; Duncan, Christine N ; Dietz, Andrew C ; Folloni Fernandes, Juliana ; Smith, Nicholas ; Dalle, Jean-Hugues ; Aubourg, Patrick ; Amartino, Hernan ; Loes, Daniel J ; Gupta, Ashish O ; Demopoulos, Laura ; Lund, Troy C ; Orchard, Paul J ; Eichler, Florian ; Thrasher, Adrian J ; Downey, Gerald F ; Gissen, Paul ; Hussain, Shaun A ; Williams, David A ; Thakar, Himal L

BACKGROUND:

Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.

METHODS:

In a phase 2-3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.

RESULTS:

A total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.

CONCLUSIONS:

At a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.).

2024-10-10·NEW ENGLAND JOURNAL OF MEDICINE

Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy

Article

作者: Dietz, Andrew C ; Colvin, Richard A ; Gupta, Ashish O ; Grzywacz, Bartosz ; Prasad, Vinod K ; Parsons, Geoffrey ; Bledsoe, Jacob R ; Eichler, Florian S ; Orchard, Paul J ; Pierciey, Francis J ; Harris, Marian H ; Downey, Gerald F ; Beckman, Amy ; Lodaya, Ankit ; Kinney, Melissa A ; Kühl, Jörn-Sven ; Slauson, Sarah ; Floro, Nicole ; Williams, David A ; Foos, Marianna ; Bonner, Melissa ; Thakar, Himal L ; Duncan, Christine N

BACKGROUND:

Gene therapy with elivaldogene autotemcel (eli-cel) consisting of autologous CD34+ cells transduced with lentiviral vector containing ABCD1 complementary DNA (Lenti-D) has shown efficacy in clinical studies for the treatment of cerebral adrenoleukodystrophy. However, the risk of oncogenesis with eli-cel is unclear.

METHODS:

We performed integration-site analysis, genetic studies, flow cytometry, and morphologic studies in peripheral-blood and bone marrow samples from patients who received eli-cel therapy in two completed phase 2-3 studies (ALD-102 and ALD-104) and an ongoing follow-up study (LTF-304) involving the patients in both ALD-102 and ALD-104.

RESULTS:

Hematologic cancer developed in 7 of 67 patients after the receipt of eli-cel (1 of 32 patients in the ALD-102 study and 6 of 35 patients in the ALD-104 study): myelodysplastic syndrome (MDS) with unilineage dysplasia in 2 patients at 14 and 26 months; MDS with excess blasts in 3 patients at 28, 42, and 92 months; MDS in 1 patient at 36 months; and acute myeloid leukemia (AML) in 1 patient at 57 months. In the 6 patients with available data, predominant clones contained lentiviral vector insertions at multiple loci, including at either MECOM-EVI1 (MDS and EVI1 complex protein EVI1 [ecotropic virus integration site 1], in 5 patients) or PRDM16 (positive regulatory domain zinc finger protein 16, in 1 patient). Several patients had cytopenias, and most had vector insertions in multiple genes within the same clone; 6 of the 7 patients also had somatic mutations (KRAS, NRAS, WT1, CDKN2A or CDKN2B, or RUNX1), and 1 of the 7 patients had monosomy 7. Of the 5 patients with MDS with excess blasts or MDS with unilineage dysplasia who underwent allogeneic hematopoietic stem-cell transplantation (HSCT), 4 patients remain free of MDS without recurrence of symptoms of cerebral adrenoleukodystrophy, and 1 patient died from presumed graft-versus-host disease 20 months after HSCT (49 months after receiving eli-cel). The patient with AML is alive and had full donor chimerism after HSCT; the patient with the most recent case of MDS is alive and awaiting HSCT.

CONCLUSIONS:

Hematologic cancer developed in a subgroup of patients who were treated with eli-cel; the cases are associated with clonal vector insertions within oncogenes and clonal evolution with acquisition of somatic genetic defects. (Funded by Bluebird Bio; ALD-102, ALD-104, and LTF-304 ClinicalTrials.gov numbers, NCT01896102, NCT03852498, and NCT02698579, respectively.).

267

项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的新闻（医药）

2025-05-14

·FiercePharma

Bluebird bio investor reluctance pays off as Carlyle, SK improve buyout offer by 67%

The new $5-per-share offer can be viewed as a win for bluebird investors, as the original deal's CVR term seems unattainable. For investors in gene therapy biotech bluebird bio, a wait-and-see approach toward a proposed acquisition has paid off.In a revised merger agreement, Carlyle and SK Capital Partners are now offering bluebird investors an option to bag $5 per share in cash. This would value the Massachusetts company at about $49 million.The new proposal is an alternative to the investment firms’ original offer, which involves $3 per share plus a contingent value right (CVR) of $6.84 per share tied to the achievement of a lofty sales milestone. “The amended offer price provides an alternative for stockholders who would prefer greater upfront cash consideration instead of the potential upside of the CVR,” the companies said in a release Wednesday.The move comes after bluebird had trouble convincing its investors to tender their shares under the original deal structure.As of close of business Monday, Carlyle and SK had received about 2.5 million bluebird shares, or 25.6% of the Massachusetts biotech’s total outstanding shares. As the number fell below the 50%-plus-one share bar required for the deal to close, the acquirer group on Tuesday extended the tender offer period to end-of-day May 28.Yet, rather than gaining more support, some investors apparently have withdrawn their shares this week. The number of tendered shares dropped below 2.3 million as of close of business on Tuesday. For bluebird investors, the new $5-per-share offer can be viewed as a win, even though it still represents a sizable discount on bluebird’s $7.04 per-share price at market close before the buyout was announced in February. To receive the $6.84-apiece CVR under the original deal, sales of bluebird’s three marketed gene therapies—Zynteglo, Lyfgenia and Skysona—need to reach $600 million over a 12-month period by the end of 2027. That goal seems very ambitious given that the company recorded just $83.8 million in 2024 total revenue. For those who don’t believe bluebird can reach $600 million sales by 2027, the new offer looks even better than a non-binding bid floated by Ayrmid but which never materialized.About a month after the original Carlyle-SK deal announcement, bluebird disclosed in late March that Ayrmid had offered to buy the company for $4.50 per share upfront, plus the same $6.84-per-share CVR. However, after three weeks of engagement, bluebird told investors that Ayrmid didn’t submit a binding proposal or obtain necessary financing to support its offer.With the new deal term, the expiration date of the tender offer has been extended by one day to May 29. Stockholders can choose between the two options, and those who have previously tendered their shares but wish to switch to the new option must withdraw and re-tender their shares. Bluebird’s board of directors unanimously approved the amended agreement. The board “continues to believe that the transaction with Carlyle and SK Capital, as amended, represents the only viable option for stockholders to receive consideration for their shares,” according to Wednesday’s joint statement.The company again urged investors to tender their shares because, absent a buyout, “bluebird is at significant risk of defaulting on its loan agreements with Hercules Capital, and it is extremely unlikely that stockholders would receive any consideration for their shares in a bankruptcy or liquidation.”According to bluebird’s annual report, a default with Hercules can be declared if bluebird fails to close the merger transaction by June 20 at the latest, subject to certain conditions.

并购

2025-04-17

·抗体圈

蓝鸟生物收购遇波折：Ayrmid 出价 “流产”

近日，基因疗法公司蓝鸟生物（bluebird bio）的收购进程陷入了戏剧性的转折。原本看似有望获得更高报价的蓝鸟生物，因爱尔兰投资公司 Ayrmid 未能按预期提交有约束力的收购要约，不得不重新回归与凯雷集团（Carlyle）和 SK 资本伙伴（SK Capital Partners）的原始交易，这一事件在生物医药投资领域引发了广泛关注。Ayrmid “爽约”，蓝鸟生物收购计划生变蓝鸟生物在基因疗法领域一直备受瞩目，然而其市场表现却不尽人意。今年 2 月，蓝鸟生物与凯雷集团和 SK 资本伙伴达成收购协议，这两家投资公司将以每股 3 美元，总计 3000 万美元的价格收购蓝鸟生物，使其私有化，交易原计划于 2025 年上半年完成。3 月下旬，Ayrmid 突然杀出，主动提出以每股 4.5 美元的价格收购蓝鸟生物，较原始报价高出 50%，并且承诺根据销售里程碑再支付每股 6.84 美元。这一出价看似诱人，给蓝鸟生物的股东们带来了更多希望。双方随后展开了为期两周的尽职调查，期间蓝鸟生物还应 Ayrmid 的要求将调查期延长了 4 天。但令人意外的是，调查结束后，Ayrmid 不仅未能提交有约束力的收购要约，还承认自身缺乏完成收购所需的资金。蓝鸟生物困境凸显，原始交易成 “救命稻草”蓝鸟生物董事会主席马克・瓦雄（Mark Vachon）表示，公司已与 Ayrmid 进行了两次接触，但均未得到有约束力或资金充足的报价。他还指出，若不能获得某种形式的资金注入，蓝鸟生物将面临贷款违约的风险。在这种情况下，蓝鸟生物董事会重申对凯雷集团和 SK 资本伙伴原始交易的支持。蓝鸟生物曾经估值颇高，在 2018 年时峰值接近 125 亿美元。尽管该公司获得了美国食品药品监督管理局（FDA）对多种基因疗法的批准，如治疗镰状细胞病的 Lyfgenia、治疗 β - 地中海贫血的 Zynteglo 以及治疗脑肾上腺白质营养不良的 Skysona，但这些疗法在市场上的接受度较低，销售缓慢，导致公司财务状况逐渐恶化。到 2025 年第一季度，蓝鸟生物的资金即将耗尽，分析师们担忧其在今年难以实现收支平衡。因此，与凯雷集团和 SK 资本伙伴的交易，成为了蓝鸟生物的 “救命稻草”。行业影响与展望：投资需谨慎，企业求突破Ayrmid 的 “爽约” 给蓝鸟生物的发展带来了不确定性，也为生物医药投资领域敲响了警钟。对于企业来说，在寻求外部投资和并购机会时，需要更加谨慎地评估潜在合作伙伴的实力和诚意；而对于投资者而言，在做出投资决策前，更要全面考量目标公司的财务状况、市场前景以及潜在风险。蓝鸟生物未来的发展仍然充满挑战，即使顺利完成与凯雷集团和 SK 资本伙伴的交易，如何提升现有基因疗法的市场表现，开发更具竞争力的产品，依旧是摆在其面前的难题。此次事件也让行业更加关注基因疗法领域的投资环境和企业的可持续发展，未来，基因疗法企业在吸引投资和实现商业成功的道路上，需要不断探索新的模式和策略。参考来源：https://www.biospace.com/deals/bluebirds-second-suitor-ayrmid-fails-to-produce-an-offer识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

基因疗法并购

2025-04-17

·Pharmaceutical Technology

Bluebird bio reaffirms Carlyle deal as Ayrmid misses deadline

bluebird has been under financial pressure for several years. Credit: SOPA Images via Getty Images. Bluebird bio (bluebird) has reaffirmed its support for a proposed acquisition by Carlyle and SK Capital after rival bidder Ayrmid failed to deliver a binding offer or secure financing by the extended deadline. The announcement marks the second time Ayrmid has initiated discussions with bluebird without producing a fully financed proposal. Bluebird said it had engaged with Ayrmid for three weeks following the private equity firm’s unsolicited bid in March, including extending the original deadline to allow more time for due diligence and deal structuring. However, Ayrmid did not submit a definitive proposal by the agreed-upon 15 April cut-off date and has yet to secure the necessary capital to proceed. As a result, bluebird’s board of directors is reiterating its unanimous support for the acquisition agreement with Carlyle and SK Capital, which was first announced in February 2025. The board is urging shareholders to tender their shares by the updated deadline of 2 May, extending the previous expiration date of 18 April. bluebird’s board chairman Mark Vachon said: “Ayrmid’s proposal remains highly conditional. bluebird has engaged with Ayrmid on two separate occasions—neither of which has resulted in a binding or fully-financed offer. The board unanimously reaffirms its support of the previously announced agreement with Carlyle and SK Capital in the strongest possible terms.” Bluebird has been under significant financial pressure for several years. The company currently faces the risk of defaulting on a $175m loan from Hercules Capital, secured in 2024 to support ongoing operations. Without a new capital injection, the board said, the company’s liquidity position remains precarious. Carlyle and SK Capital’s proposal offers $3 per share in cash, along with a potential additional payment of $6.84 per share if certain clinical and commercial milestones are met. Ayrmid‘s offer, disclosed last month, proposed $4.50 per share upfront and the same milestone-based payout structure. However, bluebird confirmed that Ayrmid has not demonstrated access to committed funding. bluebird noted that Ayrmid is continuing to seek financing and may provide further updates in the coming days. bluebird’s financial position has deteriorated over time, despite achieving several key regulatory milestones. The company currently markets three US Food and Drug Administration (FDA)- approved gene therapies – Zynteglo (betibeglogene autotemcel) for transfusion-dependent beta-thalassemia, Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy, and Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease – but has struggled with slow uptake, high costs, and reimbursement hurdles. In 2023, the company suffered a major setback when the FDA denied a priority review voucher (PRV) for Lyfgenia. Bluebird had already arranged to sell the voucher to Novartis for $103m, but the agency ruled that the therapy’s active ingredient had previously been used in Zynteglo, for which the company had already received a PRV in 2022. The loss of the expected funds deepened bluebird’s financial strain. To fill the gap, bluebird pursued emergency financing through a $150m public stock offering underwritten by Goldman Sachs and JP Morgan, as well as up to $100m in receivables financing from Alterna Capital Solutions. The company has also undergone repeated cost-cutting efforts, including workforce reductions of 30% in 2022 and an additional 25% last year. Despite these efforts, bluebird’s therapies continue to face stiff competition. Lyfgenia is priced at $3.1m per patient, while a competing treatment, Casgevy (exagamglogene autotemcel) from Vertex Pharmaceuticals and CRISPR Therapeutics, is listed at $2.2m. Both therapies were approved on the same day in December 2023 to treat sickle cell disease. Going public in 2013, bluebird has seen its stock decline sharply in recent years. Following the 16 April update, shares closed down by 7%. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here . We may still continue to send you service-related and other non-promotional communications. For more information relating to our privacy practices, we invite you to review our privacy policy .

并购优先审批上市批准细胞疗法基因疗法

100 项与 Elivaldogene Autotemcel (Bluebird Bio) 相关的药物交易

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研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肾上腺脑白质营养不良	欧盟	bluebird bio, Inc.	2021-07-16
肾上腺脑白质营养不良	冰岛	bluebird bio, Inc.	2021-07-16
肾上腺脑白质营养不良	列支敦士登	bluebird bio, Inc.	2021-07-16
肾上腺脑白质营养不良	挪威	bluebird bio, Inc.	2021-07-16

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02698579 \| NCT01896102 (ALD-102, Pubmed \| N Engl J Med) 人工标引	临床2/3期	肾上腺脑白质营养不良	32	Elivaldogene autotemcel (eli-cel) gene therapy	網網醖齋獵蓋艱鏇壓鏇(衊遞鬱構淵構簾築範壓) = 築艱網憲鑰蓋艱膚觸餘夢糧蓋窪壓範壓蓋遞夢 (築觸餘鬱鏇蓋鏇糧觸鹽 ) 更多	积极	2024-10-10
NCT03852498 \| NCT01896102 (ALD-104, Tandem Meetings ASTCT and CIBMTR2024) 人工标引	临床2/3期	肾上腺脑白质营养不良 CD34+	67	Elivaldogene Autotemcel	簾鬱獵網糧襯獵衊夢製(鹽窪積範廠製醖鏇鬱獵) = Few SAEs were reported during mobilization/apheresis; incidence was expectedly higher in conditioning and neutropenic periods, consistent with myeloablative transplant. No patients developed sinusoidal obstruction syndrome or new seizures; all survived to hospital discharge. As of Sep 6, 2023, 5 patients who received eli-cel were subsequently diagnosed with myelodysplastic syndrome. 壓築鹹網憲壓選壓積繭 (積淵構積蓋鏇壓範範觸 )	积极	2024-02-01
NCT03852498 \| NCT01896102 (ALD-104, Tandem Meetings ASTCT and CIBMTR2022)	N/A	肾上腺脑白质营养不良	-	Elivaldogene Autotemcel (eli-cel; Lenti-D) Gene Therapy	艱夢構繭齋醖鹽衊鹹壓(齋襯糧艱艱壓繭鬱鹽憲) = 2 events occurred in ALD-104 醖築構製製齋夢齋鹹製 (繭廠築鏇觸鬱蓋遞襯廠 ) 更多	积极	2022-03-01
NCT01896102 (ALD-102, BusinessWire) 人工标引	临床2/3期	肾上腺脑白质营养不良	32	Elivaldogene Autotemcel	繭餘顧鹹餘憲積餘衊願(顧獵廠糧夢窪窪構襯觸) = 鹽糧窪襯繭蓋蓋鬱築範餘憲積膚遞襯蓋餘夢積 (鑰醖鬱壓繭範鏇鹹鹽鹽 ) 更多	积极	2021-03-15
EUCTR2011-001953-10-DE \| NCT01896102 (EBMT2018)	临床2/3期	肾上腺脑白质营养不良 ABCD1	21	Lenti-D gene therapy	醖憲衊網簾觸鹹繭鹽糧(鬱淵蓋簾膚積鏇願夢遞) = 選憲選餘獵積餘廠構鹹窪鑰構網鹽積簾鹽顧壓 (廠艱構鏇壓獵蓋糧夢鏇 ) 更多	积极	2018-09-24
NCT01896102 (STARBEAM, Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床2/3期	肾上腺脑白质营养不良	17	elivaldogene tavalentivec	膚鑰網鏇製糧鏇艱積艱(鏇築壓醖淵淵製鬱構顧) = 餘窪鏇築淵遞製顧糧醖襯蓋鏇積艱觸蓋鏇鏇憲 (簾襯蓋選構鬱膚衊鬱夢 )	积极	2017-10-26