Last update 21 Nov 2024

Betibeglogene autotemcel

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Gene therapy, Hematopoietic stem cell therapy

Synonyms

2009 EGT-produced vector, Autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiglobin BB305 lentiviral vector encoding the beta-A-T87Q-globin gene, Autologous CD34+ cells encoding βA-T87Q-globin gene

+ [12]

Target

β-globin

Mechanism

β-globin stimulants(Hemoglobin beta chain stimulants), Gene transference

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

ThalassemiaBeta-ThalassemiaAnemia, Sickle Cell

Inactive Indication

Transfusion-dependent Beta ThalassemiaTransfusion-dependent Thalassemia

Originator Organization

bluebird bio, Inc.

Active Organization

bluebird bio, Inc.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

EU (29 May 2019),

Transfusion-dependent Beta Thalassemia

RegulationPRIME (EU), Accelerated assessment (EU), Accelerated Approval (EU), Rare Pediatric Disease (US), Orphan Drug (EU), Fast Track (US), Breakthrough Therapy (US), Priority Review (US), Regenerative Medicine Advanced Therapy (US)

Clinical Trials associated with Betibeglogene autotemcel

JPRN-jRCTc071190041 / Not yet recruitingPhase 2IIT

A single-arm, open-label, phase 2 study of autologous CD34+ stem cells-selected transplantation for severe systemic sclerosis - A single-arm, open-label, phase 2 study of autologous CD34+ stem cells-selected transplantation for severe systemic sclerosis

Start Date04 Jan 2019

Sponsor / Collaborator-

EUCTR2017-001275-23-GB / Unknown statusPhase 2IIT

Efficacy and safety of a cryopreserved formulation of autologous CD34+ haematopoietic stem cells transduced ex vivo with EFS lentiviral vector encoding for human ADA gene in subjects with Severe Combined Immunodeficiency (SCID) due to Adenosine Deaminase Deficiency

Start Date21 Sep 2017

Sponsor / Collaborator

Great Ormond Street Hospital Children's Charity

NCT03207009 / CompletedPhase 3

A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age

This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.

Start Date08 Jun 2017

Sponsor / Collaborator

bluebird bio, Inc.

100 Clinical Results associated with Betibeglogene autotemcel

100 Translational Medicine associated with Betibeglogene autotemcel

100 Patents (Medical) associated with Betibeglogene autotemcel

Literatures (Medical) associated with Betibeglogene autotemcel

01 Nov 2024·The Lancet

Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial

Article

Author: Walters, Mark C ; Kwiatkowski, Janet L ; Tao, Ge ; Locatelli, Franco ; Elliot, Heidi ; Hongeng, Suradej ; Lee, Ji ; Thakar, Himal L ; Thuret, Isabelle ; Kulozik, Andreas E ; Sauer, Martin G ; Yannaki, Evangelia ; Ali, Shamshad ; Thompson, Alexis A ; Lal, Ashutosh ; Thrasher, Adrian J ; Lodaya, Ankit ; Colvin, Richard A ; Kunz, Joachim B

BACKGROUNDTransfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.METHODSHGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA. Patients with β⁰/β⁰, β⁰/β^+IVS-I-110, or β^+IVS-I-110/β^+IVS-I-110 genotypes, clinically stable TDT, and a transfusion history of at least 100 mL/kg per year of packed red blood cells (pRBCs) or at least eight transfusions of pRBCs per year in the 2 years before enrolment were eligible for participation. After undergoing HSPC mobilisation and busulfan-based, pharmacokinetic-adjusted myeloablative conditioning, patients were infused with beti-cel and followed up for 24 months. The primary efficacy outcome was transfusion independence, defined as weighted average haemoglobin level of 9 g/dL or above without pRBC transfusions for 12 or more months. The primary outcome was measured in all patients who received an infusion of beti-cel (transplant population); safety was evaluated in all patients who initiated study treatment (intention-to-treat population). Patients were eligible to enrol in the ongoing 13-year long-term follow-up study (for a total of 15 years), LTF-303 (registered at ClinicalTrials.gov, NCT02633943). This trial, HGB-212, was registered at ClinicalTrials.gov (NCT03207009), and is complete.FINDINGSFrom June 8, 2017, to March 12, 2020, 20 patients were screened for eligibility. One patient was ineligible and one withdrew consent before HSPC mobilisation and myeloablative conditioning. Of the 18 patients who received beti-cel, ten (56%) were male and eight (44%) were female; 13 (72%) were younger than 18 years at the time of informed consent, and five (28%) were older than 18 years. 12 (67%) patients had β⁰/β⁰ genotypes, three (17%) had β⁰/ β^+IVS-I-110, and three (17%) had β^+IVS-I-110/β^+IVS-I-110. As of Jan 30, 2023, all patients enrolled in the long-term follow-up study and the median follow-up was 47·9 months (range 23·8-59·0). All 18 patients were evaluable for transfusion independence, with 16 (89%) of 18 reaching and maintaining transfusion independence to last follow=up (estimated effect size 89·9% [95% CI 65·3-98·6]). All patients had at least one adverse event after beti-cel infusion. There were no serious adverse events considered to be related to beti-cel, and no deaths.INTERPRETATIONThese data demonstrate that beti-cel can allow patients with genotypes that cause severe β-thalassaemia (β⁰/β⁰, β⁰/β^+IVS-I-110, or β^+IVS-I-110/β^+IVS-I-110) to reach transfusion independence. Beti-cel offers the potential to attain near-normal haemoglobin levels for those with severe forms of TDT, and a potentially curative option without the risks and limitations of allogeneic HSPC transplantation. Patients are being followed up for a total of 15 years to assess the durability of transfusion independence and long-term safety profile of beti-cel.FUNDINGBluebird Bio, Somerville, MA, USA.

01 May 2024·Blood Reviews

Revolutionising healing: Gene Editing's breakthrough against sickle cell disease

Review

Author: Strouboulis, John ; Dimitrievska, Marija ; Nicolaides, Kypros H ; Jacków-Malinowska, Joanna ; Shangaris, Panicos ; Miccio, Annarita ; El Hoss, Sara ; Bansal, Dravie ; Vitale, Marta

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.

01 May 2024·Current Opinion in Ophthalmology

Systemic medications for sickle cell disease and potential applications for sickle cell retinopathy

Review

Author: Garg, Anupam K ; Scott, Adrienne W

Purpose of reviewTo review the literature evaluating systemic medications for treatment of sickle cell disease (SCD) and their applications for sickle cell retinopathy.Recent FindingsPrior studies have demonstrated the efficacy of traditional systemic therapies in reducing the risk of development of sickle cell retinopathy. Since 2017, several new and promising disease-modifying therapies for sickle cell disease have been approved for clinical use, including the first genetic therapies such as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel). These treatments have shown promising results for systemic management but are not widely utilized due to limited access and high cost. The efficacy of these therapies for the prevention of sickle cell retinopathy remains unknown and opens the door to new avenues for research. Furthermore, the role of systemic therapy for the management of hemoglobin SC (HbSC) disease, which has milder systemic effects but higher likelihood of causing retinopathy, remains poorly understood.SummaryHydroxyurea has been a mainstay of systemic management of SCD with prior work suggesting its ability to reduce the likelihood of developing retinopathy. There are several new and potentially curative systemic therapies for SCD, though their role in retinopathy prevention and management has not been studied extensively. Future studies are necessary to understand the implications of these emerging therapies for sickle cell retinopathy.

243

News (Medical) associated with Betibeglogene autotemcel

15 Nov 2024

·www.biopharmadive.com

Halozyme bids for Evotec; BeiGene gets a new name

Today, a brief rundown of news involving Evotec, Bluebird bio and the company formerly known as BeiGene, as well as updates from Leerink Partners and Abeona Therapeutics that you may have missed.Halozyme Therapeutics has made an unsolicited bid to buydrug discovery specialist Evotec for 11 euros per share in cash, an offer worth some 2 billion euros in total. In a press release, Halozyme said the combined company could offer increased scale and become a highly attractive strategic partner to the drug industry. Evotec, in its own statement, said it would carefully analyze this expression of interest. Ned PagliaruloBluebird bio has recorded its first revenue from sales of Lyfgenia, the companys gene therapy for sickle cell disease that won U.S. approval late last year. The process to prepare and receive Lyfgenia is lengthy, so only recently did the first patient actually get an infusion, at which point Bluebird books revenue for the $3.1 million therapy.Another 16 patients have started the process to receive treatment. The company is counting on climbing demand for Lyfgenia and its two other gene therapies, Zynteglo and Skysona, as it works to break even. Currently, it has enough cash to fund operations into the first quarter. Ned PagliaruloCancer drugmaker BeiGene will now operate under the name BeOne Medicines, a change that it says reflects its commitment to oncology research. The name also distances the company from its roots in China, a connection that may be less helpful as lawmakers in the U.S. increasingly view such ties as a national security risk. BeOne, which trades on the Hong Kong and Shanghai stock exchanges as well as the Nasdaq, is headquartered in California and in Switzerland. Ned PagliaruloAdaptimmune will lay off a third of its workforce in a bid to save about $300 million and break even financially in 2027, the company said Wednesday. Adaptimmune in August won U.S. clearance for its first product, a cell therapy called Tecelra for a type of soft tissue cancer. Going forward, the company will focus resources on that launch and another program in development for similar cancers, while partnering off two unrelated projects in preclinical testing. Its also shutting down a Phase 2 study in ovarian tumors.Ben FidlerLeerink Partnershas named two senior managing directors, Grant Curry and Jason Truman, to join its biopharma M&A team. Truman previously worked in a similar role at Guggenheim Securities, while Curry was a managing director at Gordon Dyal & Co. Leerink, which reemerged via a management buy-out after the collapse of SVB Financial Group,hopes to grow its M&A business. Outside of the big banks, Centerview Partners, Lazard and PJT Partners currently win the most deal business from drugmakers, according to BioPharma Dive data. Ned PagliaruloBy the end of next April, Abeona Therapeutics should know whether the Food and Drug Administration will approve its gene therapy pz-cel for a rare wound healing condition known as recessive dystrophic epidermolysis bullosa. The agency rejected pz-cel this past April, asking Abeona for more information on how its produced.The company then resubmitted its application with new information and, on Thursday, secured a target decision date of April 29, 2025 from the agency. Ned Pagliarulo '

Gene TherapyAcquisitionExecutive ChangeDrug ApprovalPhase 2

14 Nov 2024

·endpts.com

As bluebird projects more commercial demand, the biotech continues to seek cash

Bluebird reported that 17 people with sickle cell disease have started the process of receiving its gene therapy Lyfgenia. Bluebird said in its third-quarter earnings Thursday that it recognized revenue from Lyfgenia, though it did not specify how much. In total, the gene therapy biotech reported $10.6 million in revenue, but it said it expects at least double that — $25 million — next quarter. The company dosed its first sickle cell patient with Lyfgenia, the New York Times reported in September. Vertex Pharmaceuticals, which markets the gene-edited sickle cell and thalassemia therapy Casgevy, reported that it dosed its first patient in the third quarter and recorded $2 million in revenue. That patient was a 13-year-old thalassemia patient from Saudi Arabia , Vertex confirmed to Endpoints News via email. On Thursday, bluebird also said that 35 people have started the process of receiving Zynteglo, a similar therapy for thalassemia. It reported five patient starts for Skysona, a gene therapy for cerebral adrenoleukodystrophy. The biotech added it has 17 additional starts across its gene therapy portfolio scheduled for the rest of the year, along with 30 scheduled in 2025. “Patient starts more than doubled from our second to third quarter update, providing clear evidence that our commercial launches continued to accelerate,” bluebird CEO Andrew Obenshain said in a press statement. “We remain focused on securing additional cash resources to extend our runway, which we believe would enable us to achieve this vision and reach cash flow break-even in the second half of 2025.” Bluebird announced in September that it was laying off 25% of its workforce and cutting expenses by 20%. Earlier in the year, the biotech had to rework the terms of a loan with Hercules capital, and it currently has cash to fund operations into the first quarter of 2025. When asked in an analyst call about how the company was going to get more cash, CFO James Sterling said the “strategy to extend the runway includes renegotiating key contracts and other cost initiatives, and our partnership with Hercules is key in helping move those forward.” Bluebird is also at risk of being delisted from Nasdaq and is trying to implement a reverse stock split to avoid that. It’s convening a stockholder meeting on Dec. 4 to vote on the reverse stock split.

Gene Therapy

14 Nov 2024

·firstwordpharma.com

Bluebird bio needs cash injection to fund operations beyond Q1 next year

Bluebird bio revealed in its third-quarter report Thursday that it remains in a tight financial position and needs to secure more funds in order to avoid running out of cash by early 2025 — casting a shadow over otherwise encouraging signs of commercial progress for its gene therapy portfolio.The announcement puts pressure on the company to garner additional financing within the next few months to bridge the gap to its projected cash flow break-even in the second half of next year."Based on our current forecasts, which assumes continued cost saving initiatives, successfully renegotiating key contracts and continued collaborative engagement from Hercules, we expect our existing cash and cash equivalents will enable us to fund our operations into the first quarter of 2025," stated Chief Financial Officer James Sterling during the company's earnings call.This past March, bluebird inked a $175-million, five-year term loan facility with Hercules Capital, securing funding that the company said was expected to extend its cash runway for 24 months. Bluebird later announced it would let go of about a quarter of its staff in an effort to scale back operating expenses by 20% as its trio of gene therapies struggled to get off the ground.The company ended September with $118.7 million in cash and cash equivalents, including $48 million in restricted cash — a stark contrast to its 2018 position when it held $1.6 billion (see – Vital Signs: The last flight of the bluebird).Seventeen starts for LyfgeniaThe update comes amid a backdrop of third-quarter momentum. Bluebird reported 57 patient starts completed to date in 2024 across its three approved gene therapies: 35 for Zynteglo in beta-thalassemia, 17 for sickle cell disease treatment Lyfgenia (compared to only four in Q2), and 5 for Skysona in cerebral adrenoleukodystrophy. An additional 17 starts are scheduled through year-end.Tom Klima, chief commercial and operating officer, highlighted strong early indicators for 2025, noting "30 patient starts already scheduled in 2025," with the "vast majority" of those in the first quarter. He also pointed to a near-perfect conversion rate from scheduled to treated patients. "So far, it's very high… Essentially, 100% are converting to a start. The only variable is just the time."He added, "We have plans to double capacity for Lyfgenia in 2026 based on anticipated demand."Meanwhile, the company's network of qualified treatment centres (QTCs) has more than 70 locations in the US, with approximately 30 having initiated for one of its therapies. "I think the most exciting part of that is we have about 40 QTCs that are looking to start their first patients. So, I think it's a nice indicator of growth ahead," Klima said.

Gene Therapy

100 Deals associated with Betibeglogene autotemcel

External Link

KEGG	Wiki	ATC	Drug Bank
-	Betibeglogene autotemcel	B06AX	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Thalassemia	US	bluebird bio, Inc.	17 Aug 2022
Beta-Thalassemia	GB	bluebird bio, Inc.	-

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anemia, Sickle Cell	NDA/BLA	US	bluebird bio, Inc.	25 Apr 2023
Beta-Thalassemia	NDA/BLA	US	bluebird bio, Inc.	19 Apr 2022
Transfusion-dependent Beta Thalassemia	Preclinical	IS	bluebird bio, Inc.	29 May 2019
Transfusion-dependent Beta Thalassemia	Preclinical	LI	bluebird bio, Inc.	29 May 2019
Transfusion-dependent Beta Thalassemia	Preclinical	NO	bluebird bio, Inc.	29 May 2019
Transfusion-dependent Beta Thalassemia	Preclinical	EU	bluebird bio, Inc.	29 May 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03207009 (HGB-212, Literature) Manual	Phase 3	Transfusion-dependent Beta Thalassemia	18	Betibeglogene autotemcel	(nnhauiqcub) = vmgxxlzucg vfdoshwbav (lxyhauwhwh ) View more	Positive	08 Nov 2024
HGB-210 (BusinessWire) Manual	Not Applicable	Anemia, Sickle Cell	47	LYFGENIA	bmealvljzj(hgmlpvxqsx) = vgimsaytro zmokfbytij (rthqnlaeet ) View more	Positive	09 Dec 2023
FDA Manual	Phase 1/2	Anemia, Sickle Cell	45	LYFGENIA	(iwvgqpjstn) = zpjwezewxw txyovnudfe (pqmuxechxq, 71 - 97) View more	Positive	08 Dec 2023
HGB-206 (HGB-206, Tandem Meetings ASTCT and CIBMTR2022)	Phase 1/2	BB305 lentiviral vector (LVV)	-	Lentiglobin (Group A)	bkflwjezla(soyjkuwykd) = The most common SAEs in Groups A and C are shown in Table 2. Two AML events were reported in Group A, and none in Group C. krbfljands (mgpkofdlhl )	Positive	01 Mar 2022
HGB-206 (HGB-206, Tandem Meetings ASTCT and CIBMTR2022)	Phase 1/2	BB305 lentiviral vector (LVV)	-	Lentiglobin (Group C)		Positive	01 Mar 2022
NCT02906202 (Pubmed \| Br Dent J) Manual	Phase 3	Thalassemia	23	Betibeglogene autotemcel	(zsjqimisex) = wqxwngglup exqmyejbwl (gzwoplpngs ) View more	Positive	11 Dec 2021
HGB-207, HGB-212 (EHA2021)	Phase 3	Transfusion-dependent Beta Thalassemia	27	betibeglogene autotemcel gene therapy	iovzktjmnu(punqjkujpf) = thrombocytopenia, tachycardia (2 patients < 12 years of age), abdominal pain (2 patients 12-18 years of age) ynvzzkpibg (bmevhlpoqs ) View more	-	09 Jun 2021
NCT03207009 \| NCT02906202 (Northstar-3, EHA2021)	Phase 3	Transfusion-dependent Beta Thalassemia	41	BETIBEGLOGENE AUTOTEMCEL (Beti-cel)	jzorljrbdj(tcojmwwvqt) = nizbftkpzx fxqanehdmg (pkbfduesef ) View more	-	09 Jun 2021
NCT03207009 (Northstar-3, EBMT2021)	Phase 3	Transfusion-dependent Beta Thalassemia Î²0/Î²+ (IVS-I-110) genotype	1	Betibeglogene Autotemcel (Beti-Cel; Lentiglobin	(rpkbshnnpj) = grade 2, during infusion, possibly related to treatment ydpjvvlzli (clueauqboi ) View more	Positive	14 Mar 2021
NCT02906202 (EHA2020) Manual	Phase 3	Beta-Thalassemia	21	Betibeglogene autotemcel	(pikhyeakww) = stomatitis (n=12), febrile neutropenia (n=7), epistaxis (n=3), pyrexia (n=3), and veno-occlusive liver disease (n=3) opvlpzwxmi (dckjmhycit ) View more	Positive	14 May 2020
NCT03207009 (EHA2020) Manual	Phase 3	Transfusion-dependent Thalassemia	13	Betibeglogene autotemcel	upumtcsjxx(ftvxpflkup) = 9/11 pts（≥3 months） vuqoljleey (bwdcfynbdq ) View more	Positive	14 May 2020

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Betibeglogene autotemcel

Overview

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