Delving into the Latest Updates on Betibeglogene autotemcel with Synapse

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

+ [13]

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+ [2]

Inactive Indication-

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

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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.

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 Apr 2024·International Immunopharmacology

Biomimetic nanoparticles for effective Celastrol delivery to targeted treatment of rheumatoid arthritis through the ROS-NF-κB inflammasome axis

Article

Author: Wang, Bo ; Wang, Xinggao ; Shen, Jiquan ; Hou, Ruixing

Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.

278

News (Medical) associated with Betibeglogene autotemcel

10 May 2024

·www.biopharmadive.com

iTeos shares jump on TIGIT update; Acelyrin swaps CEOs

BioPharma Dive is testing out a new format rounding up smaller updates from around the industry. Have thoughts on what could make this type of story better? Drop us a line!Today, a brief rundown of news from iTeos Therapeutics, as well as notes on Gilead, Acelyrin and Bluebird bio that you may have missed yesterday:Shares in iTeos Therapeutics jumped by nearly 40% Friday morning after the biotechnology company gave an update on a clinical trial of a cancer drug combination its studying with GSK. Interim data surpassed iTeos pre-defined efficacy criteria for clinically relevant activity, the company said. The study is testing iTeos anti-TIGIT antibody together with GSKs PD-1 inhibitor Jemperli in first-line treatment of non-small cell lung cancer.Ned PagliaruloBluebird bio made national headlines in The New York Times this week with news it had collected the cells of the first patient set to undergo treatment with its sickle cell disease therapy Lyfgenia. In an earnings update Thursday, the company disclosed that, so far this year, 14 patients have started the treatment process for its other two marketed gene therapies 11 for Zynteglo, which treats severe beta thalassemia, and 3 for Skysona, approved for a rare brain disorder. Bluebird expects between 85 and 105 patient starts for its three therapies this year. Ned PagliaruloImmune drug developer Acelyrin said Thursday that founder Shao-Lee Lin has stepped down as CEO and will be replaced by current chief legal and administrative officer Mina Kim. The biotech raised $540 million in an initial public offering last year, but has lost much of its value after hitting a clinical trial setback in September. Ben FidlerGilead Sciences and partner Arcellx on Thursday afternoon disclosed the design of a Phase 3 trial they plan to run testing a CAR-T therapy in people with relapsed or refractory multiple myeloma. The therapy, dubbed anito-cel, targets a protein called BCMA, similar to the approved cell therapies Carvykti, from Johnson & Johnson, and Abecma, from Bristol Myers Squibb.Ned Pagliarulo '

Phase 3Cell TherapyExecutive ChangeImmunotherapyGene Therapy

09 May 2024

·endpts.com

Bluebird bio starts 15 patients on its three multimillion-dollar gene therapies

Bluebird bio’s stock $BLUE jumped over 20% on Thursday following its first-quarter earnings release and the announcement of 15 patients starting on its three approved gene therapies: Zynteglo, Skysona and Lyfgenia. The company wrote in its financial report that 15 patients had completed starts on its expensive gene therapies: 11 on Zynteglo for transfusion-dependent thalassemia, three on Skysona for cerebral adrenoleukodystrophy and one on Lyfgenia for sickle cell. Bluebird also expects 85 to 105 more patient starts across its portfolio this year. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Gene Therapy

09 May 2024

·firstwordpharma.com

Uptick in gene therapy uptake triggers stock bump for beleaguered bluebird

Bluebird bio’s three gene therapies may finally be gaining momentum. The biotech shared in its first-quarter earnings report that, so far this year, 15 new patients have started on one of the multimillion-dollar treatments – and it’s anticipating over 100 starts in total for 2024. Shares of bluebird jumped 15% on the news Thursday.With a market cap now hovering around $200 million, bluebird has struggled with safety concerns, submission delays, and the rollout of its gene therapy portfolio; at its peak in 2018, the biotech had $1.6 billion in cash on hand. For more analysis, see Vital Signs: The last flight of the bluebird. However, the company may have turned a corner this year. After scoring FDA approval in December for its one-time sickle-cell disease treatment Lyfgenia (lovotibeglogene autotemcel) – priced at $3.1 million – bluebird has since secured multiple outcomes-based agreements with commercial payers, and the US Centers for Medicare and Medicaid Services (CMS) has proposed to raise reimbursement rates for the therapy. One new patient has started Lyfgenia this year. Bluebird’s $2.8-million beta-thalassemia gene therapy, Zynteglo (betibeglogene autotemcel), saw 11 new patient starts, and Skysona (elivaldogene autotemcel), a $3-million treatment for cerebral adrenoleukodystrophy, had three. Approved in 2022, Zynteglo and Skysona carry middling price tags for gene replacement therapies – far less than that of Lenmeldy (atidarsagene autotemcel) from Orchard Therapeutics, the most expensive treatment at $4.25 million. For more, see Vital Signs: Shrinkflation hits the gene therapy sector.Bluebird bio reported net revenues of $18.6 million for the first quarter, a huge jump over its $2.4 million revenues for the year-ago period. While bluebird didn’t provide full-year revenue guidance, it expects between 85 to 105 new patient starts across its three gene therapies.

Gene TherapyDrug Approval

100 Deals associated with Betibeglogene autotemcel

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External Link

KEGG	Wiki	ATC	Drug Bank
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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.

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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 Thalassemia	Phase 3	FR	bluebird bio, Inc.	08 Aug 2016
Transfusion-dependent Thalassemia	Phase 3	TH	bluebird bio, Inc.	08 Aug 2016
Transfusion-dependent Thalassemia	Phase 3	-	bluebird bio, Inc.	08 Aug 2016
Transfusion-dependent Thalassemia	Phase 3	US	bluebird bio, Inc.	08 Aug 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02633943 (LTF-303, ASH2023) Manual	Not Applicable	Transfusion-dependent Beta Thalassemia	51	Betibeglogene Autotemcel	(iezhzbuwdp) = letgympspn iglmkqawjk (lkpwqjckub, -22.3 to 10.5) View more	Positive	10 Dec 2023
NCT04628585 (LTF-307, ASH2023) Manual	Not Applicable	Anemia, Sickle Cell	47	Lovotibeglogene Autotemcel	(mafftlcgyz) = yxnonfoiis urhdgwqbgm (lyixsncicj ) View more	Positive	11 Dec 2023
FDA Manual	Phase 1/2	Anemia, Sickle Cell	45	LYFGENIA	(kzrhejaudp) = slqtpbacfp amhptjdiie (lzrnxgdkhj, 71 - 97) View more	Positive	08 Dec 2023
NCT02140554 (HGB-206, Pubmed \| Br Dent J) Manual	Phase 1/2	Anemia, Sickle Cell	35	LentiGlobin	ryerbmvicz(yljebivdam) = jskgfcxztn vxgisbcnne (fyaqhdhyve ) View more	Positive	12 Dec 2021
NCT02906202 (Pubmed \| Br Dent J) Manual	Phase 3	Thalassemia	23	Betibeglogene autotemcel	(lprhntsymb) = twpdbksjpe ltexmmstzq (qerkietqpl ) View more	Positive	11 Dec 2021
NCT02906202 (EHA2020) Manual	Phase 3	Beta-Thalassemia	21	Betibeglogene autotemcel	(jdbcocpriu) = stomatitis (n=12), febrile neutropenia (n=7), epistaxis (n=3), pyrexia (n=3), and veno-occlusive liver disease (n=3) ngjcfgatiz (ebryvuzngq ) View more	Positive	14 May 2020
HGB-207 (Northstar-2), HGB-212 (Northstar-3) (EHA2021)	Phase 3	Transfusion-dependent Beta Thalassemia	41	BETIBEGLOGENE AUTOTEMCEL (Beti-cel)	xtttagqplc(dewdfvmhyb) = dgmqpbsvor cqypczwxno (lhbbffjqap ) View more	-	09 Jun 2021
HGB-206 \| HGB-210 (BusinessWire) Manual	Not Applicable	Anemia, Sickle Cell	47	LYFGENIA	avwksefwfg(kypjhfjhyt) = sdsrvgdgxr vhurmedlag (qaibqgvivz ) View more	Positive	09 Dec 2023
NCT03207009 (EHA2020) Manual	Phase 3	Transfusion-dependent Thalassemia	13	Betibeglogene autotemcel	efcqmlmeuo(kwhbmsgjaq) = 9/11 pts（≥3 months） gmkdlteuiq (xaydmaxmit ) View more	Positive	14 May 2020
NCT02140554 (HGB-206, Pubmed) Manual	Phase 1/2	Anemia, Sickle Cell	9	Lovo-cel (Group A)	azydsvfgkw(zbjejztttm) = usrityazjf uqpcgxtozc (fskaunwzvp ) View more	Positive	25 Sep 2022
NCT02140554 (HGB-206, Pubmed) Manual	Phase 1/2	Anemia, Sickle Cell	9	Lovo-cel (Group B)	azydsvfgkw(zbjejztttm) = fljooggmmg uqpcgxtozc (fskaunwzvp ) View more	Positive	25 Sep 2022