Zynteglo (betibeglogene autotemcel) / Genetix Biotherapeutics - LARVOL DELTA

2026 Update on Clinical Trials in β-Thalassemia. (PubMed, Am J Hematol) - "Luspatercept and mitapivat have demonstrated clinically meaningful improvements in hemoglobin levels and reduction of transfusion burden and are now approved in multiple jurisdictions. Additional pyruvate kinase activators, such as etavopivat, are undergoing clinical evaluation...Approved therapies, including betibeglogene autotemcel and exagamglogene autotemcel, have achieved high rates of durable transfusion independence, while emerging platforms aim to further improve efficacy, safety, and accessibility. At the same time, several promising approaches targeting fetal hemoglobin induction, iron metabolism, and ineffective erythropoiesis have failed to demonstrate sufficient clinical benefit despite preclinical proof of concept, highlighting the complexity of therapeutic development in β-thalassemia. Future priorities include refining patient selection, generating real-world and comparative effectiveness data, developing clinically meaningful response criteria, expanding..."

Journal • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Pediatrics

Mitapivat (Aqvesme) for thalassemia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Beta-Thalassemia • Genetic Disorders

BETIBEGLOGENE AUTOTEMCEL STEM CELL COLLECTION IN THREE Β-THALASSEMIA PATIENTS (EHA 2026) - "Background Betibeglogene autotemcel (beti-cel) is an autologous gene-therapy product requiring robust mobilization and collection of CD34 ⁺ hematopoietic stem cells. Summary/Conclusion Across three diverse patients, mobilization using G-CSF with plerixafor produced good CD34 ⁺ yields for beti-cel manufacturing. These findings support the reliability of standard mobilization and apheresis protocols for robust gene-therapy collections in β - thalassemia major and E- β thalassemia patients."

Clinical • Beta-Thalassemia • Gene Therapies • Genetic Disorders • CD34

What is the formula for commercial success of a gene therapy? Reflections on approved GTx (ASGCT 2026) - "Indication selection: Commercial success across Casgevy®, Vyjuvek®, Elevidys® and Zolgensma® reinforce five criteria that appear pivotal for gene therapy success...Beqvez® (hemophilia B) appears to have treated no patients between FDA approval (2024) and market withdrawal (2025), while Hemgenix® treated 12 patients in its first year (<0.1% penetration). Uptake has also remained minimal for Zevaskyn® and Zynteglo® (beta-thalassemia).By contrast, Elevidys® (DMD) treated approximately 900 patients in the US within two years of FDA approval, although it did not receive EU authorization... The number of clinical study initiations increased continuously over the observation period, rising by 430% from 27 ongoing company sponsored programs in 2016 to 143 in 2025. After steady growth until 2021, development activity accelerated markedly from 2022 onward, with the pipeline almost doubling between 2022 and 2023. After a peak in 2024,..."

Gene therapy • Beta-Thalassemia • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Ophthalmology • Rare Diseases

A RT-qPCR assay for precise detection and absolute quantification of the T87Q β-globin variant in erythroid progeny of lentivirus transduced human CD34+ cells (ASGCT 2026) - "Despite the FDA approval of β-globin gene therapies, Lyfgenia and Zynteglo, a reliable companion diagnostic for the vector-encoded gene product is lacking. Conclusion This assay provides a precise, sensitive, and quantitative method to measure βT87Q globin expression in erythoid progeny of LVV transduced CD34+ hematopoietic stem cells. By integrating these results with hematological metrics, like total hemoglobin, this companion diagnostic assay could define the expression thresholds necessary for treatment efficacy, and has the potential to become a simple prognostic benchmark for monitoring patient outcomes in T87Q β-globin gene therapies."

Gene Therapies • Hematological Malignancies • Leukemia • CD34 • RPL13A

Avatrombopag in Refractory Thrombocytopenia Post Gene Therapy for Transfusion Dependent Thalassemia (ASPHO 2026) - " A 9-year-old female with transfusion-dependent beta thalassemia (TDT), underwent gene therapy with betibeglogene autotemcel (beticel)...Considering the possibility of thrombocytopenia, therapy was initiated with steroid burst (2 mg/kg/day × 5 days) followed by intravenous immunoglobulin (1 g/kg × 3), and rituximab (375 mg/m2 × 4)... This case demonstrates the potential utility of avatrombopag in managing refractory thrombocytopenia following gene therapy especially for TDT patients who receive frequent transfusions. The sustained platelet response suggests that TPO agonist may represent a valuable therapeutic option for patients with delayed platelet recovery."

Gene therapy • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Thrombocytopenia

Current therapeutic landscape of β-thalassemia: focus on gene therapy. (PubMed, Ther Adv Rare Dis) - "In recent years, the therapeutic landscape for TDT has changed dramatically with the approval of two autologous gene therapies in the United States: betibeglogene autotemcel (beti-cel) and exagamglogene autotemcel (exa-cel)...Gene therapy requires myeloablative busulfan-based conditioning chemotherapy, which carries the risk of short- and long-term toxicities...In this review, we discuss the available clinical trial and real-world data for beti-cel and exa-cel. We describe how gene therapy fits into the current treatment landscape and introduce areas of ongoing investigation to improve access to transformative therapy for TDT."

Journal • Review • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Pediatrics • Transplantation

Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders. (PubMed, J Blood Med) - "In this review, we discuss each of the six therapies that now have regulatory approval for treatment in the United States: Roctavian (valoctocogene roxaparvovec) for hemophilia A, Beqvez (fidanacogene elaparvovec) and Hemgenix (etranacogene dezaparvovec) for hemophilia B, Lyfgenia (lovotibeglogene autotemcel) for sickle cell disease, Zynteglo (betibeglogene autotemcel) for β-thalassemia, and Casgevy (exagamglogene autotemcel) for either sickle cell disease or β-thalassemia. Overall, results are very encouraging, often freeing patients from the need for coagulation factor or red blood cell (RBC) infusions, albeit that for some of these diseases there is room for further improvement in terms of safety and therapeutic durability, which may be achieved with next-generation gene therapy products. However, improvements are needed to address issues with durability of results, side effects, and accessibility of these therapies."

Journal • Review • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases • Sickle Cell Disease

Orsini Now Distributing Gene Therapies LYFGENIA, ZYNTEGLO, SKYSONA (PRNewswire)

Commercial • Beta-Thalassemia • CNS Disorders • Genetic Disorders • Sickle Cell Disease

Accelerating Access to Gene Therapy: Lessons from Commercial Implementation in Sickle Cell Disease and Transfusion-Dependent Thalassemia (TCT-ASTCT-CIBMTR 2026) - "With >700 patient-years of follow-up, beti-cel (Zynteglo; US approval Aug-2022) and lovo-cel (Lyfgenia; US approval Dec-2023) are now in routine use. This real-world analysis is the first to show that national-scale delivery of commercial gene therapy is feasible within a coordinated ecosystem. Coverage policies indicate broad access across public and private payers. These findings offer a functioning model for gene therapy implementation."

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

Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia. (PubMed, Blood) - P | "No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. These findings establish beti-cel as a durable, one-time therapy that achieves TI, restores iron balance, and improves quality of life, offering a potentially curative treatment option for people with TDT."

Journal • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Oncology • Transplantation

CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges. (PubMed, Mol Ther Nucleic Acids) - "Since then, the US FDA has approved nearly 30 new viral gene therapy programs, with notable examples including Zolgensma, Spinraza, Hemgenix, Zynteglo, Lyfgenia, Kymriah, Skysona, and Tecelra...In this review, we examine the range of these therapeutics and their viral carriers, focusing primarily on LVs and AAVs. We provide a snapshot of the current status of the field and highlight some of the current challenges in the clinical application of gene therapy, with particular emphasis on viral CRISPR-Cas-based technologies and their future potential."

Journal • Review • Gene Therapies • Genetic Disorders

Early post-marketing safety signals of CRISPR-edited exagamglogene autotemcel (Casgevy) versus lentiviral betibeglogene autotemcel (Zynteglo): A faers disproportionality study, 2014–2025 (ASH 2025) - "This first FAERS-based safety analysis of CRISPR-edited therapy suggests Casgevy may be associated with early post-infusion gastrointestinal/mucosal and bleeding events, while Zynteglo shows a broader haematologic and vascular signal profile, with isolated liver and immune AEs. These disproportionate reporting signals, although preliminary, support enhanced clinical vigilance, especially for mucosal toxicity and bleeding. Limitations include small case counts, underreporting biases in FAERS, absent exposure denominators, and potential misclassification from manual PT grouping."

Clinical • P4 data • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Sickle Cell Disease

An automated platform for lentiviral transduction for HSC gene therapy promotes fitness of hematopoietic stem cells combined with higher transduction efficiency (ASH 2025) - "Although therapies for HSC gene therapy have been recently approved (Zynteglo™, Lyfgenia™ and Casgevy®), still certain challenges remain associated with high costs, scalability and safety related to leukemic events. Notably, low-density lipoprotein receptor (LDL-R), the cellular receptor that serves for the recognition by the VSV glycoprotein, was accordingly upregulated in cells processed on the CliniMACS Prodigy. These results suggest that the CliniMACS Prodigy promotes higher stemness or better fitness of HSCs while simultaneously allowing for higher transduction efficiencies due to downregulation of immune related pathways and upregulation of cholesterol and sterol binding."

Gene therapy • IO biomarker • Dyslipidemia • Gene Therapies • Immunology • Infectious Disease • CD34 • TLR8

Accelerating access to gene therapy: Lessons from commercial implementation in sickle cell disease and transfusion-dependent thalassemia (ASH 2025) - "With >700 patient-years of follow-up in clinical trials, Zynteglo (approved Aug 2022 for thalassemia) and Lyfgenia (approvedDec 2023 for sickle cell disease) are now in real-world use in the United States. This real-world analysis is the first to characterize commercial gene therapy implementation,demonstrating scalable delivery and accelerated access over time. Cross-program learning andcentralized support enabled faster treatment across a national network. With published payer coveragefor >250M lives – without a single ultimate denial – these findings offer a functioning model for genetherapy implementation."

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

Rapid immune reconstitution in patients with transfusion-dependent thalassemia following betibeglogene autotemcel: A real-world experience (ASH 2025) - "These therapies use single-agent busulfanmyeloablative conditioning (Bu-MAC) and CD34+ selected autologous gene-modified hematopoietic stemcells (GM-HSCs) depleted of T cells. These findings suggest that patients with TDT treated with beti-cel are functionallylymphocyte replete 3 months after Bu-MAC and infusion of CD34+ selected GM-HSCs and remain sothereafter. Three months after infusion, patients possessed sufficient lymphocyte subset counts andPHA-induced T cell proliferation responses suggesting that patients may not require further monitoringor prophylaxis for viral reactivation. Patients also had B and T cell subsets associated with generatingprotective vaccine responses signaling potential vaccine-readiness at this time."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Infectious Disease • Tetanus • CD27 • CD8 • CXCR5

Improvement in Iron Burden in Patients with Transfusion-Dependent β-Thalassemia (TDT) Treated with Betibeglogene Autotemcel (Beti-cel) Gene Therapy: Up to 9 Years of Follow-up (ASH 2023) - P, P1/2, P3 | "Safety of beti-cel treatment largely reflected the known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. In this analysis with up to 9 years of follow up, patients treated with beti-cel who achieved TI also demonstrated sustained improvements in iron burden, and the majority of patients were able to stop chelation. Collectively, these results demonstrate the long-term durability and stability of response after beti-cel gene therapy in patients with TDT."

Clinical • Gene therapy • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Pediatrics

Sustained Efficacy, Safety, and Improved Quality of Life in Adult and Pediatric Patients with Transfusion-Dependent β-Thalassemia up to 9 Years Post Treatment with Betibeglogene Autotemcel (Beti-cel) (ASH 2023) - P, P1/2, P3 | "Five patients experienced serious veno-occlusive liver disease; all 5 received defibrotide and recovered. Beti-cel is a potentially curative gene therapy for patients with TDT across ages and genotypes through achievement of TI and normal or near-normal Hb. These data will inform real-world beti-cel treatment decisions for patients with TDT and providers."

Clinical • HEOR • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hepatology • Pediatrics • Thrombocytopenia • CD34

Gene Therapies for Hemoglobinopathies: Efficacy, Cell Collection & Transfusion Support. (PubMed, Transfus Med Rev) - "The U.S. Food and Drug Administration (FDA) has approved GTs for both SCD and TDT: lovotibeglogene autotemcel (Lyfgenia) and exagamglogene autotemcel (Casgevy) in 2023 for SCD and betibeglogene autotemcel (Zynteglo) in 2022 and exagamglogene autotemcel (Casgevy) in 2024 for TDT. This article appraises the studies the FDA approvals were based upon, with comments on transfusion and stem collection regimens. The latter aspects highlighting variability in practice and the need for additional studies to optimize pretransfusion regimens and the collection process for successful GT."

Journal • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Sickle Cell Disease • Transplantation

Betibeglogene Autotemcel (beti-cel) Gene Addition Therapy Results in Durable Hemoglobin a Production with up to 10 Years of Follow-up with Transfusion-Dependent β-Thalassemia (ASH 2024) - P, P1/2, P3 | "Conclusion : These data provide evidence of the sustained favorable benefit-risk profile of gene addition therapy with beti-cel in participants with TDT and will inform real-world treatment decisions. Beti-cel is a potentially curative gene addition therapy for patients with TDT across genotypes and ages through achievement of durable TI, normal or near-normal Hb, and a favorable long-term safety profile with up to 10 years of follow-up."

Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Pediatrics

Curative Therapies for Hemophilias and Hemoglobinopathies in Adults: Immune, Gene, and Stem Cell Approaches in a Global Context. (PubMed, Biomedicines) - "Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide."

Journal • Review • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases • Sickle Cell Disease • Transplantation

MAXIMIZING SAFETY AND EFFICACY IN HEMATOPOIETIC STEM CELLS GENE THERAPY (EHA 2025) - "Background: Although therapies for HSC gene therapy have been recently approved (Zynteglo™, Lyfgenia™ and Casgevy®), still certain challenges remain associated with high costs, scalability and safety related to leukemic events. Based on these results, we propose a combined strategy of transduction enhancers and the use of Baboon envelope pseudotyped LV on the automated CliniMACS Prodigy platform to achieve significantly higher transduction efficiencies and enhanced engraftment."

Clinical • Gene therapy • Gene Therapies • CD34 • FLT3

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

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

Post-Approval, Real-World Experience with Betibeglogene Autotemcel for Transfusion-Dependent Beta Thalassemia (TCT-ASTCT-CIBMTR 2025) - "Patients received beti-cel after conditioning with single-agent PK-adjusted busulfan over four days...He received eculizumab due to elevated sc5b-9 without other thrombotic microangiopathy criteria, eventually engrafting platelets with romiplostim support after 82 days... Our experience demonstrates consistent achievement of RBC transfusion independence in patients with TDT receiving commercial beti-cel. Patients experienced prolonged platelet engraftment time and high platelet transfusion requirements, which were associated with severe bleeding in patients with VOD or HLA Class I alloimmunization. Further studies will seek to mitigate bleeding complications by reducing VOD rates and to explore the impact of HLA Class I alloimmunization in patients receiving beti-cel for TDT."

Clinical • Real-world • Real-world evidence • Beta-Thalassemia • Genetic Disorders • Hepatology • Subarachnoid Hemorrhage • Thrombocytopenia • CD34