Casgevy (exagamglogene autotemcel) / Vertex, CRISPR Therap, Molecular Templates - LARVOL DELTA

ToolGen Files Patent Infringement Lawsuit Against Vertex in the United Kingdom (PRNewswire) - "ToolGen...announced today that it has filed a patent infringement lawsuit in the United Kingdom against Vertex Pharmaceuticals and its commercial manufacturing partners, Lonza and RoslinCT, regarding Vertex's genome editing therapy CASGEVY....It provides a novel treatment for patients with sickle cell disease and beta-thalassemia. The one-time treatment is reportedly priced at approximately £1.7 million (approx. $2.2 million USD), with sales projections indicating blockbuster potential....'This lawsuit is not aimed at restricting patient access to CASGEVY in the United Kingdom. Rather, it seeks to ensure ToolGen is properly acknowledged and rewarded through a fair licensing agreement.'"

Patent • Beta-Thalassemia • Sickle Cell Disease

APHERESIS EXAGAMLOGENE AUTOTEMCEL, EXA-CEL, (CASGEY) GENE THERAPY IN TRANSFUSION DEPENDENT THALASSEMIA (TDT): FIRST UK EXPERIENCE (EBMT 2025) - "CD34+ cell collection is with filgrastim/plerixafor priming. Despite some logistical challenges and potential risks, we have established a process to safely administer high-doses of GCSF and plerixafor, and effectively collect a high yield of CD34+ cells, maximising the chances of successful Exa-cel manufacturing. Effective management of this process will allow us to optimise our strained capacity and avoid re-harvest of patients. Further experience needs to be obtained and prospectively data collected to evaluate practice."

Gene therapy • Anemia • Gene Therapies • Genetic Disorders • Hematological Disorders • BCL11A • CD34

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

Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease (clinicaltrials.gov) - P3 | N=26 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: Feb 2025 ➔ Jun 2027 | Trial primary completion date: Feb 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

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

DURABLE CLINICAL BENEFITS IN TRANSFUSION-DEPENDENT Β-THALASSEMIA WITH EXAGAMGLOGENE AUTOTEMCEL (EBMT 2025) - P2/3 | "For the 3 pts who did not achieve TI12 in CLIMB-111, 2 achieved TI12 in CLIMB-131 (duration transfusion free: 23.0 and 15.7mos), while 1 stopped transfusion for 4.8mos. Durable transfusion independence was achieved in >94% of pts receiving exa-cel, with associated clinically meaningful and sustained increases in HbF and total Hb for up to 5yrs of available follow-up. Exa-cel's safety profile remains consistent with busulfan myeloablation and autologous transplantation. These findings confirm exa-cel's potential as a one-time functional cure for patients with TDT."

Clinical • Beta-Thalassemia • Genetic Disorders • Neutropenia • Oncology • CD34

DURABLE CLINICAL BENEFITS IN SEVERE SICKLE CELL DISEASE WITH EXAGAMGLOGENE AUTOTEMCEL (EBMT 2025) - P2/3 | "Elimination of VOCs was achieved in 90% of pts receiving exa-cel, with clinically meaningful increases in HbF and total Hb that were maintained over time. Exa-cel's safety profile remains consistent with myeloablative busulfan conditioning and autologous transplantation. These findings confirm the potential of exa-cel as a one-time functional cure for patients with severe SCD."

Clinical • Genetic Disorders • Hematological Disorders • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Sickle Cell Disease • CD34

GENE THERAPY FOR SICKLE CELL DISEASE AND TRANSFUSION DEPENDENT BETA THALASSEMIA: REAL WORLD DATA, SINGLE CENTER EXPERIENCE (EBMT 2025) - "Informed consents were obtained.For SCD patients, hydroxyurea (HU) was stopped 2 months prior to stem cell collection, and RBC exchange sessions were conducted every 2-3 weeks for 2 months before apheresis aiming to reduce hemoglobin S (HbS) levels <30% and hemoglobin (Hb) concentration ≤11 g/dL... Intensive Iron chelation was carried out for TDT patients.Exagamglogene autotemcel Infusion: Two patients ( 13 and 16 year old children) with TDT were treated with Exagamglogene autotemcel. Busulfan was given every 6 hours for 4 days and adjusted to achieve a cumulative AUC of 71 mg/L and 84 mg/L ,respectively... Our center's experience demonstrates the feasibility of gene therapy for treating patients with hemoglobinopathies, with successful patient preparation, stem cell collection, and infusion protocols. The CD34+ cell collection process for SCD remains challenging and requires further optimization and adoption of newer protocol. While the outcomes are promising,..."

Clinical • Gene therapy • Real-world • Real-world evidence • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hepatology • Mucositis • Sickle Cell Disease • Thrombocytopenia • CD34

GENE THERAPY FOR SICKLE CELL DISEASE AND TRANSFUSION DEPENDENT BETA THALASSEMIA: REAL WORLD DATA, SINGLE CENTER EXPERIENCE (EBMT 2025) - "Informed consents were obtained.For SCD patients, hydroxyurea (HU) was stopped 2 months prior to stem cell collection, and RBC exchange sessions were conducted every 2-3 weeks for 2 months before apheresis aiming to reduce hemoglobin S (HbS) levels <30% and hemoglobin (Hb) concentration ≤11 g/dL... Intensive Iron chelation was carried out for TDT patients.Exagamglogene autotemcel Infusion: Two patients ( 13 and 16 year old children) with TDT were treated with Exagamglogene autotemcel. Busulfan was given every 6 hours for 4 days and adjusted to achieve a cumulative AUC of 71 mg/L and 84 mg/L ,respectively... Our center's experience demonstrates the feasibility of gene therapy for treating patients with hemoglobinopathies, with successful patient preparation, stem cell collection, and infusion protocols. The CD34+ cell collection process for SCD remains challenging and requires further optimization and adoption of newer protocol. While the outcomes are promising,..."

Clinical • Gene therapy • Real-world • Real-world evidence • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hepatology • Mucositis • Sickle Cell Disease • Thrombocytopenia • CD34

PREPARING NURSING STAFF FOR THE ADMINISTRATION OF THE FIRST GENE-EDITED STEM CELL INFUSION: A COMPREHENSIVE APPROACH (EBMT 2025) - "The ministry of national guard health Affairs (MNGHA)-Riyadh is the first authorized treatment center in Saudi Arabia to treat SCD and TDT patients with exagamglogene autotemcel and the first center globally administered the gene edited stem cells outside of clinical trials.At our institution, we developed a comprehensive training program to prepare our nursing staff to administer the gene edited stem cells to our first patients.This abstract describes the training program developed to ensure that the nursing staff are well-prepared to infuse the Gene edited stem cells safely.The cells will be provided in vial and the entire volume of each vial should be infused via syringe within 20 minutes of thawing and through a central venous catheter which presents a challenge in completing the infusion in a timely manner without delay or interruption... A well-structured and comprehensive training program for nurses, including educational sessions, in-service training, and mock..."

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

Abu Dhabi introduces gene-editing therapy for sickle cell disease for first time in UAE (The Gulf Today) - "The Department of Health - Abu Dhabi (DoH), the regulator of the healthcare sector in the emirate, has announced the introduction of CASGEVY, the first CRISPR/Cas9 gene-editing therapy in the UAE...This achievement opens new horizons and offers innovative treatment for patients suffering from sickle cell disease (SCD) and transfusion dependent beta-thalassemia (TDT), positioning Abu Dhabi as a leading destination for life sciences and is a significant achievement in the field of innovation and gene therapies...The innovative treatment, provided by Abu Dhabi Stem Cells Center (ADSCC), in coordination with DoH and in collaboration with Vertex Pharmaceuticals, a leading biotechnology company. The first patient is scheduled to begin the groundbreaking therapy at Yas Clinic Hospital in April of this year."

Launch non-US • Sickle Cell Disease

Assessing the Impact of Exagamglogene Autotemcel (Exa-cel) on Health Inequalities in Patients with Sickle Cell Disease in the United Kingdom and Canada (ISPOR 2025) - "In the UK and Canada, the DCEA methodology provides a quantitative approach to estimate how exa-cel may significantly lower health inequality, which is an important element for HTA bodies to incorporate into healthcare decision making."

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

Comparing Ex-Vivo and In-Vivo Administration in CRISPR-Based Gene Therapies for Beta-Thalassemia: A Cost-Effectiveness Analysis (ISPOR 2025) - "The ex-vivo CRISPR therapy exagamglogene autotemcel (exa-cel) was recently approved by the National Institute for Health and Care Excellence (NICE) under a managed access agreement... In-vivo CRISPR offers cost savings, reduced patient burden, and improved cost-effectiveness compared to ex-vivo therapy. However, these results depend on assumptions regarding in-vivo efficacy and safety. Future research should address uncertainties as in-vivo CRISPR trial data emerge."

Cost effectiveness • Gene therapy • HEOR • Preclinical • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders

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

Solution structure of the Z0 domain from transcription repressor BCL11A sheds light on the sequence properties of protein-binding zinc fingers. (PubMed, Protein Sci) - "Non-DNA-binders show a depletion of polar residues at the positions expected to contact nucleotides and increased sequence divergence, making these domains more likely to be annotated as atypical, degenerate, or to be missed as zinc fingers. We anticipate these sequence patterns will help distinguish DNA-binders from non-binders, an open problem in the functional understanding of zinc-finger motifs."

Journal • Beta-Thalassemia • 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

Recommendations [Google translation] (Danish Medicines Council) - "The Danish Medicines Council recommends exagamglogene autotemcel (exa-cel) for the treatment of severe sickle cell disease (SCD) in patients ≥ 12 years of age with recurrent episodes of pain (vaso-occlusive crises, VOC) for whom hematopoietic stem cell transplantation is suitable and where a human leukocyte antigen-matched related stem cell donor is not available...The Danish Medicines Council recommends exagamglogene autotemcel (exa-cel) for the treatment of the blood disease transfusion-dependent β-thalassemia (TDT) in patients ≥ 12 years of age for whom hematopoietic stem cell transplantation is suitable and where a human leukocyte antigen-matched related donor is not available....The Danish Medical Council recommends vadadustat for the treatment of symptomatic anemia (anemia) associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis."

Reimbursement • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Sickle Cell Disease

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

Bahrain Makes History with First Successful CRISPR-Based Sickle Cell Treatment Outside the US (GlobeNewswire) - "The Bahrain Oncology Centre (BOC) has made medical history by successfully treating a sickle cell disease (SCD) patient using CRISPR-based gene-editing therapy, Casgevy (exagamglogene autotemcel). This marks the first successful treatment of its kind outside the United States, positioning Bahrain as a global leader in precision medicine and innovative healthcare solutions...'As the clinical team responsible for delivering this groundbreaking treatment, we are honoured to bring CRISPR-based therapy to patients in Bahrain and beyond.'"

Launch non-US • Sickle Cell Disease

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

Vertex Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Fourth Quarter 2024 Results...Product revenue increased 16% to $2.91 billion compared to the fourth quarter of 2023, primarily driven by the continued performance of TRIKAFTA/KAFTRIO. Net product revenue increased 17% to $1.84 billion in the U.S...The multiple ascending dose (MAD) portion of the Phase 1/2 study of VX-522, a nebulized CFTR mRNA therapy, is underway, with data expected in the first half of 2025; Vertex has completed enrollment of children 5 to 11 years of age with SCD or TDT in two global Phase 3 studies of CASGEVY and expects to complete dosing of this age group in 2025; Vertex continues to enroll and dose patients with primary AMKD in the Phase 3 portion of the AMPLITUDE global Phase 2/3 pivotal clinical trial of inaxaplin...Vertex expects to complete enrollment in the interim analysis cohort in 2025 and apply for potential accelerated approval in the U.S. after this cohort reaches 48 weeks of treatment, assuming a positive interim analysis."

Commercial • P1/2 data • Trial status • Beta-Thalassemia • Cystic Fibrosis • Renal Disease • Sickle Cell Disease

A CRISPR/Cas approach to β-haemoglobinopathies (PubMed, Med Sci (Paris)) - "More than 70 patients with severe β-thalassemia and sickle cell disease have been treated with the Casgevy® therapy. Most have achieved a significant improvement of clinical phenotype, with high editing efficiency in hematopoietic cells associated with normal or near normal hemoglobin levels. While the long-term safety and efficacy of this powerful approach still need to be evaluated, new strategies are being developed to further improve therapeutic outcomes, reduce potential genotoxicity and lower the costs of therapy."

Journal • Review • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Vertex Announces CASGEVY Reimbursement Agreement for the Treatment of Sickle Cell Disease in England (Businesswire) - "Vertex Pharmaceuticals...announced today a reimbursement agreement with NHS England for eligible sickle cell disease (SCD) patients to access the CRISPR/Cas9 gene-edited therapy, CASGEVY (exagamglogene autotemcel). The reimbursement agreement comes as the National Institute for Health and Care Excellence (NICE) issues positive guidance recommending CASGEVY’s use in the NHS. It means that eligible SCD patients in England now have access to the therapy following the prior agreement for transfusion-dependent beta thalassemia (TDT) patients announced last August."

NICE • 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

Durable Clinical Benefits in Severe Sickle Cell Disease with Exagamglogene Autotemcel (TCT-ASTCT-CIBMTR 2025) - "Elimination of VOCs was achieved in 90% of pts receiving exa-cel, with clinically meaningful increases in HbF and total Hb that were maintained over time. Exa-cel’s safety profile remains consistent with myeloablative busulfan conditioning and autologous transplantation. These findings confirm the potential of exa-cel as a one-time functional cure for patients with severe SCD."

Clinical • Genetic Disorders • Hematological Disorders • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Sickle Cell Disease • CD34