Lyfgenia (lovotibeglogene autotemcel) / bluebird bio - LARVOL DELTA

Maximizing Safety and Efficacy in Hematopoietic Stem Cell Gene Therapy (ASGCT 2025) - "Although new treatments for hematopoietic stem cell (HSC) gene therapy have been recently approved for several diseases such as beta-thalassemia (Zynteglo), sickle cell disease (Lyfgenia and Casgevy), and adrenoleukodystrophy (Skysona), a certain number of challenges still remain such as the high costs and scalability associated with these therapies, as well as the increased safety concerns regarding the related leukemic events. Experiments to investigate the mechanisms involved in better performance of LV transduction on the automated platform, including detailed molecular analysis of gene expression pathways by Next Generation Sequencing (NGS), are ongoing. Disease Focus of Abstract:Other Other: Rare diseases of the blood such as (but not limited to) hemoglobinopathies"

Clinical • Gene therapy • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Rare Diseases • Sickle Cell Disease • CD34 • FLT3

Cost-Effectiveness of Gene Therapy for Sickle Cell Disease in Uganda: Tailoring High-Income Evidence to Uganda's Context (ASGCT 2025) - "To estimate lifetime SoC costs in Uganda, we employed a Markov model designed to simulate the progression of patients across three health states: (1) standard of care (SoC) without hydroxyurea, (2) SoC with fixed dose hydroxyurea, and (3) death...Application of lovo-cel (bluebird bio) or exa-cel (Vertex Therapeutics) gene therapy for SCD was targeted to the same patient populations for authorized use in the U.S. and Europe: eligible individuals with SCD aged 12 years and older who meet specific trial inclusion criteria...2023) is lower than the scaled cost of a SCD gene therapy product in this model, suggesting a profit margin is possible for a locally manufactured gene therapy product for the treatment of SCD in Uganda. Disease Focus of Abstract:Sickle Cell"

Cost effectiveness • Gene therapy • HEOR • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • SCD

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials. (PubMed, Adv Ther) - "Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials."

Journal • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

A Targeted Literature Review of Value-Based Agreements (VBAs) for Cell and Gene Therapies in the United States (ISPOR 2025) - "The therapies with VBAs in place included: Beqvez, Casgevy, Hemgenix, Kymriah, Luxturna, Lyfgenia, Roctavian, Vyjuvek, Zolgensma, and Zynteglo... In this review, multiple VBAs for CGTs were identified across multiple disease areas. Most payers did not publicly disclose which outcomes measures the VBAs were assessing. Of those that did, outcomes assessed could be sourced from routine patient visits and/or adjudicated claims, placing no additional burden on providers to collect data for the sole purpose of the VBA."

Gene therapy • Review • Gene Therapies

Payment Models for Sickle-Cell Disease Gene Therapies in Colorado Medicaid: Real-World Data Analysis (ISPOR 2025) - "The introduction of exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel) required a comprehensive evaluation of potential payment strategies.Description: To inform this decision, Colorado Medicaid analyzed real-world data from the Health Care Policy & Financing database, focusing on the costs associated with severe SCD patients from 2018 to 2023. The significance of real-world data was emphasized in identifying eligible patient populations and determining the actual costs of SoC. Furthermore, the analysis pointed out that the duration of contracts has a significant impact on financial outcomes."

Clinical • Gene therapy • Medicaid • Real-world • Real-world evidence • Reimbursement • US reimbursement • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A critique review of fetal hemoglobin modulators through targeting epigenetic regulators for the treatment of sickle cell disease. (PubMed, Life Sci) - "Notably, pharmaceutical approaches like hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, in addition to therapeutic techniques like gene therapies like Casgevy and Lyfgenia, signify noteworthy advancements in the management of issues connected to SCD. It has been demonstrated that inhibiting these targets can prevent the silencing of the gene encoding for the formation of γ-chains and, in turn, increase the synthesis of HbF, providing a possible treatment option for SCD symptoms. These approaches could pave the way for innovative, mechanism-driven therapies that address the unmet medical needs of SCD patients."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Sickle Cell Disease • HIF1A • ZBTB7A

Innovative Payment Models for Sickle-Cell Disease Gene Therapies in Medicaid: Leveraging Real-World Data and Insights from CMMI's Gene Therapy Access Model. (PubMed, Pharmacoeconomics) - "The study highlights critical considerations for Medicaid in negotiating OBAs for SCD gene therapies. Achieving budget neutrality over 6 years is unlikely due to low SoC costs. However, payment models can enhance value-based spending by linking high therapy costs and potential rebates to the health gains these treatments may offer. OBAs offer offsets contingent on therapy effectiveness durability and contract terms (such as length and price), while varying eligibility criteria impact budgets and outcomes. Medicaid real-world data is crucial for navigating complexities in defining eligible populations and structuring OBAs."

Journal • Real-world evidence • Reimbursement • US reimbursement • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • SCD

Sickle cell disease gene therapy drug expenses and reimbursement: a litmus test for commercial pricing strategy and patient access for curative therapies. (PubMed, Cytotherapy) - "In the United States, following Food and Drug Administration approval, lovotibeglogene autotemcel (Lyfgenia, bluebird bio, Inc, Sommerville, MA, USA) and exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals Inc, Boston, MA, USA) were launched in 2024 for treatment of patients 12 years and older with frequent vaso-occlusive crises. Here we will discuss the first treatment with lovotibeglogene as a test case serving to highlight the multiple drug reimbursement pathways in the United States for cell and gene products for orphan disorders and their impact on patient adoption and access."

Journal • Pricing • Reimbursement • US reimbursement • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Casgevy (exagamglogene autotemcel) and Lyfgenia (lovotibeglogene autotemcel) for individuals 12 years and older with sickle cell disease (SCD) and recurrent vaso-occlusive crises (VOC): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG). (PubMed, Genet Med Open) - No abstract available

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Comparative Analysis of CRISPR-Cas9, Lentiviral Transduction, and Base Editing for Sickle Cell Disease Therapy in a Murine Model (TCT-ASTCT-CIBMTR 2025) - "The FDA approved Casgevy® and Lyfgenia TM for patients with SCD 2,3...Edited SCD CD34+ HSPCs were infused into busulfan conditioned NBSGW mice (n = 5 mice for each technique, including a non-edited group as a control and a group infused with a 1:1:1 mixture of all three products)... Ex vivo analysis of the infused cells showed ∼95% editing of BCL11A enhancer, ∼75% base editing at β-globin, and a vector copy number (VCN) of ∼0.9 copies/diploid genome. At 16 weeks of transplantation, bone marrow (BM) analyses showed similar human CD45+ cell engraftment frequencies across all groups (22-94%). In engrafted mice, there was 95.8% BCL11A editing and 62.8% β-globin base editing."

Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • PTPRC

Clinical Outcomes of Lenti/G-βAS3-FB Lentiviral Vector Gene Therapy for Sickle Cell Disease (TCT-ASTCT-CIBMTR 2025) - "This treatment involves the collection of patients’ stem cells, ex vivo gene transfer using the Lenti/G-βAS3-FB vector, and subsequent myeloablative marrow conditioning with busulfan prior to the re-administration of the gene-modified stem cells...She was not receiving hydroxyurea or chronic transfusions...They received plerixafor-mobilized peripheral blood stem cells with poloxamer transduction enhancer instead of bone marrow, along with the modified GLOBE AS3-FB vector to reduce proviral size...In December 2023, the U.S. Food and Drug Administration approved two effective treatments for sickle cell disease, Casgevy and Lyfgenia. Given this, we have ethically decided to close the study to future enrollment. Nonetheless, the insights gained will inform future gene therapy investigations."

Clinical • Clinical data • Gene therapy • Viral vector • Bone Marrow Transplantation • Cardiovascular • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Mucositis • Sickle Cell Disease • CD34

Streamlining the Coordination of Advanced Cellular and Gene Therapies: A Checklist Approach for Transplant Coordinators (TCT-ASTCT-CIBMTR 2025) - "Methods, Intervention, & Analysis Adapted from the design of a pre-existing coordination checklist for autologous/allogeneic stem cell transplant, 3 additional checklists were developed for Omisirge cord transplant, Zynteglo and Lyfgenia gene therapies. This tool can allow for standardization to prevent any oversight in the coordination process. The checklist can be revised as processes and additional therapies are initiated to assist with coordination and developing the plan of care."

Gene therapy • Metastases • Bone Marrow Transplantation • Gene Therapies • Transplantation

An Update on Lovotibeglogene Autotemcel (Lovo-cel) Clinical Trials for Sickle Cell Disease (SCD) and Analysis of Early Predictors of Response to Lovo-Cel (TCT-ASTCT-CIBMTR 2025) - P1/2, P3 | "One-time lovo-cel treatment results in sustained HbA T87Q production and eliminated VOEs and sVOEs in a majority of participants. Models developed in this post hoc analysis enable prediction of the likelihood of VOE-CR and sVOE-CR using measurements as early as 6 months post lovo-cel infusion."

Clinical • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Maximizing Safety and Efficacy in Hematopoietic Stem Cell Gene Therapy (TCT-ASTCT-CIBMTR 2025) - "Hematopoietic stem cell (HSC) gene therapy has been recently been aproved for beta-thalassemia, sicklce cell disease, and adrenal leukodystrophy, specifcially Lyfgenia ™ ,Casgevy ™ , Skysona TM, . Based on these results, we propose a combined strategy of transduction enhancers and the use of Baboon envelope pseudotyped LV on the automated platform to achieve significantly higher transduction efficiency. Ongoing experiments to investigate the mechanisms involved in better performance of LV transduction on the automated platform, validating BaEV pseudotyped LV on the automated platform, including detailed molecular analysis of gene expression pathways by Next Generation Sequencing (NGS), are underway."

Clinical • Gene therapy • Beta-Thalassemia • Gene Therapies • Hematological Disorders • Sickle Cell Disease • CD34

Multi-Disciplinary Care Model for Transition and Re-Transition after Gene Therapy in Sickle Cell Disease (ASH 2024) - "This led to the Food and Drug Administration (FDA) approval of the lentiviral-based gene addition product (lovotibeglogene autotemcel) and CRISPR-Cas9 based gene editing product (exagamglogene autotemcel) for patients with SCD above 12 years of age. Our team's collaborative approach to SCD care with sickle cell specialists, transplant team and other care providers and CBO continues into the long term follow up period, including ongoing supportive services for both patients and their families. Conclusion : As newer therapies are developed and approved for transformative SCD care, development of a transitional model with early engagement of an interdisciplinary team is critical for empowering sickle cell warriors and for their successful transition back into the community."

Gene therapy • Bone Marrow Transplantation • Fatigue • Gene Therapies • Genetic Disorders • Hematological Disorders • Mood Disorders • Pain • Psychiatry • Sickle Cell Disease

Participants with a History of Stroke in Lovotibeglogene Autotemcel (Lovo-cel) Clinical Trials (ASH 2024) - P, P1/2, P3 | "Longer follow-up will be required to understand the impact on neurovasculature and risk of stroke recurrence. These data will help inform real-world lovo-cel treatment recommendations and decisions for those with SCD and their care providers."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Ischemic stroke • Sickle Cell Disease • Vascular Neurology

An Update on Lovotibeglogene Autotemcel (Lovo-cel) Clinical Trials for Sickle Cell Disease (SCD) and Analysis of Early Predictors of Response to Lovo-Cel (ASH 2024) - P, P1/2, P3 | "Conclusions : One-time lovo-cel treatment results in sustained HbAT87Q production and eliminated VOEs and sVOEs in a majority of participants. Models developed in this post hoc analysis enable prediction of the likelihood of VOE-CR and sVOE-CR using measurements as early as 6 mo post treatment."

Clinical • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Ernest Beutler Lecture and Prize (ASH 2024) - "In the last year, both globin gene addition (lovo-cel) and CRISPR gene editing (exa-cel) therapies received FDA approval. Dr. John Tisdale will summarize recent advances in ex vivo modification of hematopoietic stem cells for both lentiviral gene and CRISPR gene editing therapies for the hemoglobin disorders, concentrating on clinical parameters and prospects for improving preconditioning and moving toward strategies that would allow application without the need for hospitalization and intensive supportive care."

Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • BCL11A

HGB-210: A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease (clinicaltrials.gov) - P3 | N=35 | Active, not recruiting | Sponsor: bluebird bio | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Viral vector • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

Transformative Therapies for Sickle Cell Disease: A Global Stakeholder Perception Study on Advanced Cell Therapies (ASH 2024) - "Exagamglogene autotemcel(EA) was the preferred gene therapy (20%), followed by lovotibeglogene autotemcel(L) (16.7%), 63.3%had no preference. It highlights fertility preservation, access to QTC, risk of secondary malignancy and cost barriers critical factors in patient selection. Future research should focus on expanding the donor pool for HSCT, gathering long-term data on GT's safety and efficacy, and developing strategies to alleviate the financial burden associated with these TT."

Clinical • Metastases • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Oncology • Pain • Pediatrics • Sickle Cell Disease

Maximizing Safety and Efficacy in Hematopoietic Stem Cell Gene Therapy (ASH 2024) - "Hematopoietic stem cell (HSC) gene therapy has been recently successfully employed for certain rare blood disorders including hemoglobinopathies, which resulted even in marketing authorizations such as Lyfgenia™ and Casgevy™. Based on these results, we propose a combined strategy of transduction enhancers on the automated platform to achieve significantly higher transduction efficiency. Ongoing experiments investigate the mechanisms involved in better performance of lentiviral transduction on the automated platform with molecular analysis via Next Generation Sequencing (NGS) and respective bioinformatics analysis."

Clinical • Gene therapy • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

Transformative Gene Therapies for Sickle Cell Disease Exagamglogene Autotemcel and Lovotibeglogene Autotemcel (ASHP 2024) - No abstract available

Gene therapy • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Finding a Way for Patients to Access Gene Therapies (ISPOR-EU 2024) - "Out of 9 funded single-administration GTx (eladocagene exuparvovec, etranacogene dezaparvovec, betibeglogene autotemcel, valoctocogene roxaparvovec, voretigene neparvovec, exagamglogene autotemcel, lovotibeglogene autotemcel, atidarsagene autotemcel, onasemnogene abeparvovec), RSAs were identified in the US (n=7), UK (n=5), Canada (n=3), and Australia (n=2)... To manage uncertainties around long-term benefits and financial impact, local decision-makers implement RSAs. Canada and UK mainly use financial-based schemes built on simple price discounts. Australia and the US aim at implementing schemes whereby treatment cost payers incur corresponds to expected health outcome for a particular patient."

Clinical • Gene therapy • Gene Therapies • Rare Diseases

bluebird bio to Present Additional Long-Term Follow-up Data from Gene Therapy Programs in Sickle Cell Disease and Beta-Thalassemia at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (Businesswire) - "bluebird bio will present updated follow-up data and analysis of early predictors and response to lovotibeglogene autotemcel (lovo-cel) in patients from HGB-206 and HGB-210 studies, demonstrating consistent clinical outcomes as early as six months post infusion and continued durability of clinical benefit of lovo-cel...The company will also present updated long-term analyses of efficacy, safety, and health related quality of life data of betibeglogene autotemcel (beti-cel) in patients with transfusion-dependent beta-thalassemia (TDT)."

P1/2 data • P3 data • Beta-Thalassemia • Sickle Cell Disease

Gene Therapies for Sickle Cell Disease. (PubMed, J Pharm Technol) - "Currently, there are 4 U.S. Food and Drug Administration (FDA)-approved drugs, including hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, which work to alleviate symptoms and prevent complications associated with SCD, albeit without addressing the underlying cause of SCD. The authors identified relevant studies and summarized the data on the two gene therapies. Exagamglogene autotemcel and lovotibeglogene autotemcel are two management strategies that address the underlying cause of SCD and provide curative potential for patients with SCD."

Gene therapy • Journal • Review • Bone Marrow Transplantation • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease • Transplantation