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

MTE #24: Gene Therapies and Hepatotoxicity (Ticketed) (AASLD 2026) - "Multiple gene therapies have been approved in recent years by the US Food and Drug Administration (FDA) for a variety of inherited disorders, including: Duchenne muscular dystrophy (delandistrogene moxeparvovec-rokl, 2023) Hemophilia A (valoctocogene roxaparvovec-rvox, 2023) Hemophilia B (etranacogene dezaparvovec-drlb, 2022; fidanacogene elaparvovec-dzkt, 2024) Spinal muscular atrophy (onasemnogene abeparvovec-brve, 2025) Sickle cell disease (exagamglogene autotemcel, 2023)...Identify clinically available AAV gene therapy treatments. Discuss ways to identify and potentially mitigate hepatotoxicity, and to optimize care for patients and study participants receiving AAV gene therapy."

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Hepatology • Liver Failure • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases • Sickle Cell Disease

First In human Successful CRISPR/Cas9 Gene Therapy (Exagamglogene Autotemcel) in a Heart Transplant Recipient with Beta-Thalassemia Major (TTS 2026) - "Post-transplant, he was maintained on immunosuppression including tacrolimus and mycophenolate mofetil...He underwent myeloablative conditioning in Aug 2025 with intravenous Busulfan from Day -7 to Day -4, dynamically adjusted to a target AUC of 900 micromol-min/L via pharmacokinetic monitoring... This first-in-human case establishes the feasibility and safety of administering myeloablative CRISPR/Cas9-edited gene therapy in a highly immunosuppressed, recent heart transplant recipient. Curing the underlying beta-thalassemia and achieving transfusion independence definitively eliminates the primary source of iron overload, thereby protecting the cardiac allograft. Crucially, this success highlights that a history of solid organ transplantation and concurrent immunosuppression should no longer serve as exclusion criteria, paving the way for future patients with severe hemoglobinopathies to access life-saving gene therapies."

Clinical • First-in-human • Gene therapy • P1 data • Atrial Fibrillation • Beta-Thalassemia • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Genetic Disorders • Heart Failure • Hematological Disorders • Hepatology • Solid Organ Transplantation • Transplant Rejection • Transplantation • CD34

Mapping the Management-to-Cure Transition in Thalassemia Research: Semantic Topic Modeling of 17,651 Publications Across Three Decades. (PubMed, Hemoglobin) - "The first curative option, allogeneic hematopoietic stem cell transplantation (HSCT), emerged in the early 1980s; the first gene-editing therapy, Casgevy, followed in 2023, marking the latest step in this trajectory...Country-level analysis revealed marked divergence: US research focused more heavily on gene therapy (10.0% vs. 4.1% in China), while Chinese research maintained a stronger HSCT focus (6.3% vs. 4.0% in the US). These findings chart the course of a major therapeutic transition and carry direct implications for research funding allocation, global strategies for equitable access to curative therapies, and computational literature surveillance to inform clinical guideline updates."

Journal • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Transplantation

CTx001 an AAV2 Mini-CR1 Gene Therapy for dry AMD in Phase-I/II clinical trials: in-vitro and in-vivo Studies Show Potent Complement Target Engagement and Inhibition on different cellular and animal models (ESGCT 2026) - No abstract available

Gene therapy • P1/2 data • Preclinical • Dry Age-related Macular Degeneration • Gene Therapies • CR1

PRAC adopted updates to the SmPC to incorporate final clinical safety and efficacy data from studies CTX001-111, CTX001-121 and CTX001-131, the latter listed as a specific obligation in Annex II. Sections 4.8 and 5.1 of the SmPC were updated, with corresponding changes to the Package Leaflet. RMP version 2.0 was submitted, and additional updates were introduced to the product information (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 31 Aug – 3 Sep 2026: [AI generated summary]

PRAC • Beta-Thalassemia • Sickle Cell Disease

Translating CRISPR to Practice in the Clinic: Transformative Therapy in Hemoglobinopathies and Emerging Applications in Malignancies. (PubMed, JCO Oncol Pract) - "Exagamglogene autotemcel, the first clustered regularly interspaced short palindromic repeats (CRISPR)-based gene-editing therapy to enter clinical practice, has established genome editing as a curative-intent option for eligible patients with severe sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT)...In oncology, CRISPR-based therapy remains investigational, with early clinical feasibility demonstrated in relapsed or refractory B-cell malignancies, T-cell malignancies, AML, multiple myeloma, and selected solid tumors. For hematologists, oncologists, and transplant and cellular therapy programs, the central challenge is to integrate CRISPR into practice with the rigor required for any high-risk curative therapy: careful patient selection, disciplined delivery, and long-term accountability."

Journal • Review • Acute Myelogenous Leukemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Pain • Sickle Cell Disease • Solid Tumor • Transplant Rejection • Transplantation • CD34

On-target and off-target activities of CRISPR therapeutics across scales. (PubMed, Trends Biotechnol) - "These include exagamglogene autotemcel, an ex vivo therapy for hemoglobinopathies using CRISPR nuclease Cas9, and kayjayguran abengcemeran, an in vivo therapy using a protospacer adjacent motif-altered base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. In this opinion article, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing 'on-target' and 'off-target' mutational activities across the diverse contexts in which they occur."

Journal • Review • Genetic Disorders • Hematological Disorders • Metabolic Disorders

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

Recent Highlights and Outlook (GlobeNewswire) - "CASGEVY generated second quarter 2026 revenue of $76 million, representing 78% growth quarter-over-quarter and 151% growth year-over-year....CRISPR Therapeutics continues to advance its in vivo hematopoietic stem cell editing approach using lipid nanoparticle (LNP)-mediated delivery. This approach has the potential to expand the addressable patient populations for SCD and TDT."

Preclinical • Sales • Beta-Thalassemia • Sickle Cell Disease

Sickle Cell Disease: From Ancient Origins to Modern Breakthroughs in Gene Therapy. (PubMed, Biomedicines) - "Current management rests on supportive pharmacological interventions, including hydroxyurea, chronic transfusion therapy, L-glutamine, and multimodal pain management, complemented by lifestyle modifications. Curative approaches have advanced substantially: hematopoietic stem cell transplantation (HSCT) remains the established standard of cure, while the regulatory approvals in late 2023 of the CRISPR/Cas9-based exagamglogene autotemcel (Casgevy) and the lentiviral vector-based lovotibeglogene autotemcel (Lyfgenia) represent the most transformative development in the history of SCD therapeutics. This review traces the disease from its ancient origins and molecular characterization through to its clinical manifestations, inheritance patterns, screening strategies, and the full spectrum of current and emerging therapies. Persistent challenges, prohibitive treatment costs, healthcare inequities, the ethical dimensions of genome editing, and the urgent need for long-term..."

Journal • Review • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Inflammation • Malaria • Pain • Rare Diseases • Sickle Cell Disease • Transplantation • HBB

CRISPRing through time: How cutting-edge technology is revolutionizing life sciences and medicine. (PubMed, Mol Ther Nucleic Acids) - "Furthermore, a technological landmark was achieved when the Food and Drug Administration (FDA) approved the first CRISPR-based gene therapy (exa-cel) to edit erythroid specific enhancer region of BCL11A in hematopoietic stem cells, introduced in patients suffering from sickle cell anemia to achieve durable remission...Given the vast amount of information on CRISPR, we try to pin down key take-home messages for scientists as well as non-scientist readers. This review article attempts to understand why and how CRISPR remains significant and seamlessly integrates in the emerging era of new technologies."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Sickle Cell Disease

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

Journal • Beta-Thalassemia • Genetic Disorders

Supportive care, prevention, and emerging therapies for acute chest syndrome in sickle cell disease. (PubMed, Expert Rev Hematol) - "This review synthesizes data on supportive measures (fluid management, analgesia, antibiotics, oxygen/respiratory support, and transfusion), preventive interventions (incentive spirometry and nocturnal bilevel positive airway pressure), disease-modifying therapies (hydroxyurea, L-glutamine), investigational agents (therapeutic anticoagulation, inhaled nitric oxide, and pyruvate kinase activators), and recently approved gene therapies (exagamglogene autotemcel, lovotibeglogene autotemcel)...Gene therapies represent a paradigm shift toward durable or potentially curative prevention of ACS. With expanding access to these therapies, ACS may become a rare complication of SCD, although significant barriers related to cost, infrastructure, and global equity must be overcome."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Pain • Preventive care • Sickle Cell Disease

Vertex Announces US FDA Approval for Expanded Use of CASGEVY for the Treatment of People Ages 2 Years and Older With Sickle Cell Disease or Transfusion-Dependent Beta Thalassemia (Businesswire) - "CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT....CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs."

FDA approval • Beta-Thalassemia • Sickle Cell Disease

Efficacy, Safety, and Treatment-Delivery Feasibility of Autologous Gene Therapy for Sickle Cell Disease: A Systematic Review With Descriptive Synthesis of Clinical Trials. (PubMed, Eur J Haematol) - "Autologous gene therapy for SCD produces substantial short- to medium-term reductions in severe VOEs and improves hemoglobin biology, but certainty remains limited by single-arm designs, small samples, evolving protocols, and incomplete long-term follow-up. Successful delivery depends on separable processes: transfusion preparation, mobilization, apheresis collection, ex vivo manufacturing/editing, product release, conditioning, and reinfusion. Long-term safety, fertility, organ outcomes, reimbursement, and global scalability remain unresolved implementation barriers."

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

Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent ?-Thalassemia (TDT) (clinicaltrials.gov) - P3 | N=16 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: May 2026 ➔ Nov 2027 | Trial primary completion date: May 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Pediatrics

Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD) (clinicaltrials.gov) - P3 | N=13 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: May 2026 ➔ Jun 2027 | Trial primary completion date: May 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease • HP

DURABLE CLINICAL BENEFITS WITH EXAGAMGLOGENE AUTOTEMCEL FOR PEDIATRIC PATIENTS (5-11 YEARS) WITH TRANSFUSION-DEPENDENT Β‑THALASSEMIA AND SICKLE CELL DISEASE WITH RECURRENT VASO-OCCLUSIVE CRISES (EHA 2026) - "Exa-cel demonstrated benefit in children, with a safety profile consistent with busulfan myeloablative conditioning and autologous transplant. Data support exa-cel as a potential one-time functional cure for children 5-11y with TDT and SCD, with potential for additional benefit with early treatment, before chronic disease complications develop."

Clinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hepatology • Pediatrics • Sickle Cell Disease • CD34

LONG-TERM FOLLOW-UP CONFIRMS DURABLE CLINICAL BENEFITS OF EXAGAMGLOGENE AUTOTEMCEL IN TRANSFUSION-DEPENDENT B-THALASSEMIA: FINAL RESULTS OF THE CLIMB THAL-111 STUDY (EHA 2026) - "CLIMB-111 participants then enroll in long-term follow-up study CLIMB-131 for up to 15 years of follow-up after exa-cel infusion. The safety profile is consistent with busulfan myeloablative conditioning and autologous transplant. These data continue to support exa-cel as a potential one-time functional cure for TDT."

Clinical • Beta-Thalassemia • Genetic Disorders • ERFE

DURABLE CLINICAL BENEFITS WITH EXAGAMGLOGENE AUTOTEMCEL FOR OVER 6 YEARS IN PATIENTS AGED 12 TO 35 YEARS WITH SICKLE CELL DISEASE WITH RECURRENT VASO-OCCLUSIVE CRISES (EHA 2026) - "The safety profile is consistent with busulfan myeloablative conditioning and autologous transplant. These results continue to support exa-cel as a potential one-time functional cure for severe SCD."

Clinical • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Sickle Cell Disease • HP

CHANGING EPIDEMIOLOGY OF SICKLE CELL DISORDERS: GBD 2023 ANALYSIS OF INCIDENCE TRENDS TO 2023, REGIONAL DISPARITIES IN EUROPE, AND IMPLICATIONS FOR GENE THERAPY ACCESS (EHA 2026) - "With novel gene therapies (e.g., exagamglogene autotemcel) now approved in the EU and UK, up-to-date epidemiological burden data are essential for planning equitable access and resource allocation...However, persistent and widening mortality disparities across Europe highlight urgent inequities in access to comprehensive care and newly approved gene therapies. Coordinated European policies are essential to address demographic shifts from migration and to ensure equitable rollout of innovative curative treatments."

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

Global regulatory submissions to expand use of CASGEVY (Vertex Press Release) - "Vertex has also recently completed regulatory submissions in the Kingdom of Saudi Arabia and United Kingdom to expand the use of CASGEVY to younger children. Upon availability, there is an established network of activated authorized treatment centers in these countries prepared to support patients."

Filing • MHRA filing • Beta-Thalassemia • Sickle Cell Disease

Vertex Presents New Data on CASGEVY, Including First European Presentation of Data in Children Ages 5–11, at the European Hematology Association Congress… (Vertex Press Release) - "In the Phase 3 CLIMB-151 clinical study of children with severe SCD, all 11 patients dosed are free from VOCs and all 8 out of 8 (100%) patients with sufficient follow-up achieved the primary endpoint of being free from VOCs for at least 12 consecutive months (VF12). Of children achieving VF12, the mean (min, max) duration VOC-free was 19.0 (13.2, 30.1) months; In the Phase 3 CLIMB-141 clinical study of children with TDT, 15 patients have been dosed with CASGEVY, and all 8 out of 8 (100%) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin of at least 9 g/dL (TI12). All children who achieved TI12 remained so throughout the follow-up; the mean (min, max) duration transfusion independence was 23.4 (13.3, 28.5) months."

P3 data • Beta-Thalassemia • Sickle Cell Disease

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CTX001 in Healthy Adults. (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Cajal Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Exa-cel in Children with Transfusion-Dependent β-Thalassemia or Sickle Cell Disease. (PubMed, N Engl J Med) - P3 | "Exa-cel therapy resulted in transfusion independence or freedom from severe vaso-occlusive crises in participants with transfusion-dependent β-thalassemia or sickle cell disease, respectively, who were followed for at least 16 months. All the participants had grade 3 or 4 adverse events. (Funded by Vertex Pharmaceuticals and CRISPR Therapeutics; CLIMB THAL-141 ClinicalTrials.gov number, NCT05356195; CLIMB SCD-151 ClinicalTrials.gov number, NCT05329649.)."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hepatology • Sickle Cell Disease • CD34