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

Exagamglogene autotemcel (exa-cel; Casgevy) broadly and durably improved health-related quality of life (HRQOL) in adult and adolescent patients with transfusion-dependent β-thalassemia (TDT), as shown in results from the phase 1/2/3 CLIMB THAL-111 (NCT03655678) and phase 3 CLIMB THAL-131 (NCT04208529) trials (Cancer Network) - "In adult patients (n = 35), the mean baseline EQ-5D-5L visual analog scale (VAS) score and EQ-5D-5L health utility US and UK index scores were near general population norms and in line with previously reported baseline scores for adults with TDT. The minimal clinically important difference (MCID) was established to be 7 to 10 points...In adolescents (n = 19), the mean EQ-5D-Y VAS score had a mean change from baseline of 4.5 points (SD, 14.5) at month 6, and a mean change from baseline of 6.1 points (SD, 16.4) at month 24."

HEOR • Beta-Thalassemia

Sickle Cell Disease and Gene Therapy Among African Americans: A Dilemma and Challenge. (PubMed, J Racial Ethn Health Disparities) - "Although the US Food and Drug Administration's recently approved groundbreaking base editing gene therapies of Casgevy and Lyfgenia have been declared promising in treating SCD, uptake for the therapies has been low. Though the treatment of SCD through gene therapy has sparked some excitement in the African American community, it is also causing a dilemma and challenges. This paper documents the dilemma and challenges associated with gene therapy among the African American SCD community and what can be done to address them."

Journal • Review • Cardiovascular • Gene Therapies • Genetic Disorders • Heart Failure • Hematological Disorders • Pain • Sickle Cell Disease

Specificity of CRISPR-Cas9 Editing in Exagamglogene Autotemcel - Update. (PubMed, N Engl J Med) - No abstract available

Journal

Gene Therapy for Sickle Cell Disease and Transfusion Dependent Beta Thalassemia: Real World Data, Single Center Experience (ICBMT 2025) - "Here we summarize our center's experience in providing Exagamglogene Autotemcel...For SCD patients, hydroxyurea (HU) was stopped 2 months before 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 Intensive Iron chelation was carried out for TDT patients...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, long-term follow-up is essential to assess the durability of these interventions."

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

Vertex Announces CASGEVY Reimbursement Agreement for the Treatment of Transfusion-Dependent Beta Thalassemia and Sickle Cell Disease in Italy (Businesswire)

Reimbursement • Beta-Thalassemia • Sickle Cell Disease

Vertex, Enlaza Launch Up-to-$2B Collaboration to Improve CASGEVY® Conditioning. (PubMed, Hum Gene Ther) - No abstract available

Journal

ToolGen Files Patent Infringement Lawsuit Against Lonza in the Netherlands (PRNewswire) - "The lawsuit charges that Lonza, in its production of Vertex's CASGEVY at its Dutch facility, infringes ToolGen's European patent (EP 4 357 457) covering CRISPR-Cas9 RNP technology."

Patent • Beta-Thalassemia • Sickle Cell Disease

Casgevy® - TDT und SCD werden heilbar. (PubMed, MMW Fortschr Med) - No abstract available

Journal

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

Improvements in Health-Related Quality of Life in Patients with Transfusion-Dependent β-Thalassemia After Exagamglogene Autotemcel. (PubMed, Blood Adv) - P2/3, P3 | "These results indicate exa-cel leads to broad, durable, and clinically-meaningful improvements in HRQoL in adults and adolescents with TDT. (CLIMB THAL-111 and 131 Clinical Trials.gov numbers, NCT03655678 and NCT04208529)."

HEOR • Journal • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Oncology • Pediatrics • Transplantation

Improvements in Health-Related Quality of Life in Patients with Severe Sickle Cell Disease After Exagamglogene Autotemcel. (PubMed, Blood Adv) - P2/3, P3 | "Exa-cel led to broad and clinically meaningful HRQoL benefits in adults and adolescents with SCD. (CLIMB SCD-121 and 131; Clinical Trials.gov numbers NCT03745287 and NCT04208529)."

HEOR • Journal • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Oncology • Pain • Pediatrics • Sickle Cell Disease • Transplantation

CTx001 an AAV2 Mini-CR1 Gene Therapy for dry AMD: IND-Enabling Studies Show Potent Complement Target Engagement and MAC Inhibition on Activated RPE Cells (ESGCT 2025) - No abstract available

Gene therapy • Dry Age-related Macular Degeneration • Gene Therapies • CR1

CLIMB SCD-121: A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease (clinicaltrials.gov) - P2/3 | N=63 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

The racial politics of visibility and equity in genome-editing therapies for sickle cell disease. (PubMed, Soc Sci Med) - "While scientists have adopted the language of social justice when discussing genome-editing therapies for sickle cell disease, the first of these treatments to be approved, Casgevy, costs approximately $2M per patient...As a result, the processes of biomedicalization that stratify access to new treatments and enable the extraction of value from Black bodies in the name of innovation are obfuscated. Ultimately, efforts to extend access to sickle cell therapies in the name of social justice are bound by socio-historical patterns of racism."

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

Vertex Reports Second Quarter 2025 Financial Results (Businesswire) - "Vertex delivered a strong quarter of revenue growth with each of our three product launches - ALYFTREK, JOURNAVX, and CASGEVY - contributing....Total revenue increased 12% to $2.96 billion compared to the second quarter of 2024, primarily driven by the continued performance of cystic fibrosis (CF) therapies and early contributions from the three ongoing launches. In the U.S., total revenue increased 14% to $1.85 billion due to continued strong patient demand and favorable gross-to-net versus prior year. Outside the U.S., total revenue increased 8% to $1.12 billion due to strong performance across multiple geographies."

Sales • Beta-Thalassemia • Cystic Fibrosis • Pain • Sickle Cell Disease

Advances in Sickle Cell Disease Treatment: A Comparative Review of Hematopoietic Stem Cell Transplantation and Gene Therapy (Casgevy and Lyfgenia). (PubMed, Stem Cells Dev) - "This milestone marks a crucial moment in the history of both SCD and gene therapies and thus warrants exploring the considerations revolving around their implementation. Although these therapies seem to offer hope for patients ineligible for HSCT, their long-term outcomes remain unassessed-further studies with extended follow-up are needed to confirm their safety and durability."

Journal • Review • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Oncology • Sickle Cell Disease • Transplantation

Third-generation novel technologies for gene editing. (PubMed, Trends Biotechnol) - "CRISPR-Cas methods using RNA-guided enzymes are the most used gene editing tools and have produced gene-edited crops (rice, wheat, corn, etc.) and human therapeutics (Casgevy, approved for commercial use; Vertex Pharmaceuticals)...Some of these limitations were partially addressed by the development of second-generation editors, including base editors (BEs) and prime editors (PEs). Third-generation gene editing technologies such as seekRNA and bridgeRNA can overcome most of these limitations and are the subject of this review."

Journal • Review

CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential. (PubMed, Cell Prolif) - "This potential was affirmed with the FDA's first approval of a CRISPR-based therapy, Casgevy, for sickle cell disease in 2023...Despite these advances, significant challenges remain, including off-target effects, delivery methodologies, immune responses, and long-term genomic safety concerns. Future improvements in editor precision, innovative delivery platforms, and enhanced safety assessments will be essential to fully integrate CRISPR-based interventions into standard clinical practice, significantly advancing personalised medicine."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Huntington's Disease • Infectious Disease • Movement Disorders • Muscular Dystrophy • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Sickle Cell Disease • Solid Tumor • PD-1

Updated Review of Current Therapeutic Approaches for the Management of Sickle Cell Disease. (PubMed, Cardiovasc Hematol Disord Drug Targets) - "There are six Food and Drug Administration (FDA)-approved drugs, hydroxyurea, L-glutamine, crizanlizumab- TMCA, voxelotor, Casgevy, and Lyfgenia, that are used for the prophylaxis and treatment of serious complications of sickle cell disease. Ongoing research seeks to enhance treatment options and develop potential cures for SCD. This review attempts to present a comprehensive overview of the current therapeutic approaches and newly developed innovative medicines to combat and potentially eradicate SCD with an emphasis on their mechanisms, efficacy, and clinical implications."

Journal • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Pain • Sickle Cell Disease • Transplantation

CRISPR-based therapeutic genome editing for inherited blood disorders. (PubMed, Nat Rev Drug Discov) - "This paradigm has been exemplified with the first US Food and Drug Administration (FDA)-approved CRISPR-Cas9 therapy for sickle cell disease and β-thalassaemia, exa-cel (Casgevy)...In this Review, we explore the state-of-the-art genome editing technologies of nucleases, base editors and prime editors, which hold promise to address unmet clinical needs for patients with inherited haematological disorders. We highlight the progress made for several disorders and discuss the challenges that remain for ex vivo and in vivo targeting of HSCs for next-generation gene therapies."

Journal • Review • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Sickle Cell Disease • Transplantation

Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/βC Genotype (clinicaltrials.gov) - P3 | N=12 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: Dec 2029 ➔ Dec 2033 | Trial primary completion date: Dec 2029 ➔ Dec 2033

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

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

DURABLE CLINICAL BENEFITS AND IMPROVEMENT OF TISSUE IRON OVERLOAD WITH EXAGAMGLOGENE AUTOTEMCEL FOR TRANSFUSION-DEPENDENT THALASSEMIA (EHA 2025) - "CLIMB-111 pts then enroll in long-term follow-up study CLIMB-131 for up to 15 yrs of follow-up. Exa-cel demonstrated durable clinical benefit in adults and adolescents with TDT and a safety profile consistent with busulfan myeloablative conditioning and autologous transplant. After exa-cel infusion, storage iron can be successfully removed by IRT with no evidence of iron reaccumulation after cessation of IRT. This suggests that in addition to durable transfusion independence, exa-cel has the potential to prevent tissue iron deposition, eliminating the need for chronic IRT, and may preserve end-organ function."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

DURABLE CLINICAL BENEFITS WITH EXAGAMGLOGENE AUTOTEMCEL FOR SICKLE CELL DISEASE WITH RECURRENT VASO-OCCLUSIVE CRISIS AND FACTORS IMPACTING CD34+ HEMATOPOIETIC STEM CELL COLLECTION (EHA 2025) - "Exa-cel has the potential to provide a one-time functional cure for SCD. This is the largest data set analyzed to date describing single-agent plerixafor M/A collection characteristics of SCD pts. Younger age and blood CD34+ cells/µL at baseline and pre-apheresis correlated most strongly with higher CD34+ HSPC collection; no evidence of correlation was observed for measures of disease severity or blood HbS level."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • CRP • HP

Progress in bringing CASGEVY to patients (Vertex Press Release) - "Through reimbursement agreements, Vertex has secured access for eligible SCD or TDT patients in multiple countries including Austria, Bahrain, England, the Kingdom of Saudi Arabia, Northern Ireland, Scotland, the United Arab Emirates, the United States and Wales. Vertex is continuing to work with government and reimbursement authorities globally to secure sustainable access for additional eligible patients."

Reimbursement • Anemia • Beta-Thalassemia • Sickle Cell Disease