Hemgenix (etranacogene dezaparvovec-drlb) / uniQure, CSL Behring - LARVOL DELTA

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

A Paradigm Shift in Hemophilia Care: The Promise of Gene Therapy. (PubMed, Curr Gene Ther) - "Gene therapy has shown new possibilities in hemophilia, with many patients achieving near-normal levels of clotting factors and experiencing a significant reduction in bleeding episodes. However, challenges remain, including potential declines in Factor VIII levels over time, immune responses to viral vectors, and high treatment costs. Ongoing research is focused on improving durability, expanding eligibility, and exploring alternative delivery methods."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults With Hemophilia B With Pretreatment Adeno-associated Virus Serotype 5 (AAV5) Neutralizing Antibodies (Nabs) (clinicaltrials.gov) - P3 | N=35 | Recruiting | Sponsor: CSL Behring | Trial completion date: Oct 2028 ➔ Apr 2032

Trial completion date • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

IX-TEND 3004: Phase 3, Open-label, Single-dose Study of CSL222 in Adolescent Male Subjects (≥ 12 to < 18 Years of Age) With Severe or Moderately Severe Hemophilia B (clinicaltrials.gov) - P3 | N=18 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

IX-TEND 3004: Phase 3, Open-label, Single-dose Study of CSL222 in Adolescent Male Subjects (≥ 12 to < 18 Years of Age) With Severe or Moderately Severe Hemophilia B (clinicaltrials.gov) - P3 | N=18 | Not yet recruiting | Sponsor: CSL Behring

New P3 trial • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Sustained disease correction is achieved without long-term vector-related liver toxicity four years after etranacogene dezaparvovec hemophilia gene therapy both in individuals with and without early transaminitis (ESGCT 2025) - No abstract available

Clinical • Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hepatology • Rare Diseases

A single dose expression and biodistribution study in non-human primates supports dosing of etranacogene dezaparvovec in adolescent Haemophilia B patients. (ESGCT 2025) - No abstract available

Clinical • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

IThe AIFA Board of Directors approves the reimbursability of 11 medicines, including the first gene therapy for haemophilia B (Italian Medicines Agency) - "The National Health Service will reimburse the first one-shot treatment for severe and moderately severe haemophilia B, a rare and potentially fatal disease that causes bleeding in the joints, muscles and internal organs. At its meeting on 29 July, the AIFA Board of Directors gave the green light to the reimbursability of Hemgenix (etranacogene dezaparvovec), the first gene therapy authorised for haemophilia B, which can have a significant impact on patients' quality of life. Currently, people with this hereditary blood clotting disorder must undergo continuous, lifelong infusions of coagulation factor IX to compensate for the congenital deficiency and prevent bleeding....Voydeya (danicopan), a new oral medicine to be used in combination in adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have residual haemolytic anaemia."

Reimbursement • Hemophilia B • Paroxysmal Nocturnal Hemoglobinuria

NHS treats first haemophilia B patient with gene therapy (Progress Educational Trust (PET)) - "The first haemophilia B patient has been treated with gene therapy on the NHS...The patient is a 44-year-old man from Newcastle who had been diagnosed with Haemophilia B at 18 months old. He received a single dose of Hemgenix (also known as etranacogene dezaparvovec) administered through an hour-long infusion at Guy's and St Thomas' Hospital in London....It is the most expensive drug available via the NHS, with a list price of £2.6 million per dose, although the NHS has arranged an undisclosed discount with the manufacturer."

Reimbursement • Hemophilia B

First German haemophilia B patient receives gene therapy HEMGENIX (PharmaTimes) - "The first haemophilia B patient in Germany has been treated with the one-time gene therapy HEMGENIX at the Hemophilia Treatment Center at Hannover Medical School, CSL Behring Germany has announced...HEMGENIX is the first gene therapy of its kind approved in Europe for adults with severe and moderately severe haemophilia B....CSL Behring has introduced HEMGENIX in Germany under a novel success-based reimbursement model."

Launch Europe • Hemophilia B

Fitusiran (Qfitlia) for hemophilia A and B. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

First UK patient treated with CSL Behring’s gene therapy for Haemophilia B (Pharmafile) - "CSL Behring has announced that the first patient in the UK has received HEMGENIX (etranacogene dezaparvovec) through the NHS, marking a significant milestone in haemophilia B treatment and NHS access to gene therapies...The treatment was administered at Guy’s and St Thomas’ NHS Foundation Trust in London to a patient from the North East of England. HEMGENIX is the first and only gene therapy for haemophilia B recommended by NICE via its Single Technology Appraisal and the first made available through a managed access agreement under the Innovative Medicines Fund....CSL Behring will continue working with NHS England to ensure broader access to the treatment across the UK."

Launch non-US • Hemophilia B

Evaluation of One-Stage Assays for the Monitoring of Recombinant Human Factor IX Padua Activity After Etranacogene Dezaparvovec Gene Therapy. (PubMed, Haemophilia) - "FIX activity differences between central and local OSAs were modest; similar differences were observed in vitro with rhFIX-wt versus rhFIX-Padua. Commonly available OSAs can be used to monitor patients post-etranacogene dezaparvovec administration; we recommend using the same assay platform throughout the post-treatment period."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Galicia Becomes First in Spain to Approve Gene Therapy for Hemophilia B (Born2Invest) - "The President of the Xunta, Alfonso Rueda, announced on Monday that the regional government of Galicia has approved an investment of €15.6 million for the purchase of the first gene therapy drugs for treating hemophilia B....He emphasized that the tender for the supply of the drug Etranacogene Dezaparvovec, a gene therapy treatment for the hereditary blood coagulation disorder, affirms 'the validity of public health' and positions Galicia as 'the first community in Spain to treat hemophilia B with gene therapy.'"

Financing • Hemophilia B

First Data from the American Thrombosis and Hemostasis Network Transcends Registry Hemophilia Gene Therapy Outcomes Arm (ISTH 2025) - P | "Background Adeno-associated viral vector (AAV)-mediated gene therapy for hemophilia B (HB) and hemophilia A (HA) is a reality for patients since conditional approval for marketing of etranacogene dezaparvovec-drlb and fidanacogene elaparvovec-dzkt for HB, and valoctocogene roxaparvovec-rvox for HA. Three participants required steroid treatment for vector-induced transaminitis. Table or Figure Upload"

Gene therapy • Cardiovascular • Dermatology • Fatigue • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Pain • Rare Diseases • Thrombosis • Urticaria

Long-term safety and efficacy of etranacogene dezaparvovec in haemophilia B (IX-TEND-3003 study) (ISTH 2025) - P, P2, P3 | "Study design, timelines and enrolment status will be presented. Table or Figure Upload"

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

First French real-world gene therapy experience with etranacogene dezaparvovec for hemophilia B (ISTH 2025) - "No patient received corticosteroids to treat post-infusion ALT elevation. No additional FIX infusion were required."

Clinical • Gene therapy • Real-world • Real-world evidence • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

AMT-060 etranacogene dezaparvovec in haemophilia B: duration of freedom from bleeding & prophylaxis (ISTH 2025) - P1/2, P2, P3 | "All (100%) participants from phase 1/2 and phase 2b studies remained free of continuous FIX concentrate prophylaxis up to their respective data cut (8- and 5- years post-treatment); all studies combined 59/60 (98%) remained free of continuous prophylaxis during the current follow-up. Table or Figure Upload"

Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Gene Therapy in Hemophilia B: Innovative Methods to Evaluate Value Contribution (ISTH 2025) - "Aims To assess the value of etranacogene dezaparvovec (ED) versus long-acting recombinant factor IX (LA) for the treatment of severe and moderately severe Hemophilia B (sHB) in Spain from the perspective of clinical experts...ED was perceived to provide a high therapeutic impact (3.6±0.9), supported by high-quality evidence (4.0±1.4) and potential cost savings in direct (1.3±2.3) and indirect (1.7±1.8) healthcare expenditures as there would be a reduction in hospitalisations and a potential increase in patients’ productivity. Clinicians perceived that the single dose and diminished annual bleeding rate resulted in a superior QoL (1.9±1.5)."

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Etranacogene dezaparvovec in haemophilia B: a 48-month post hoc responder analysis of HOPE-B (ISTH 2025) - P3 | "No genotoxicity due to AAV integration or late hepatotoxicity was observed, including in participants with transient early transaminase increases or prior chronic viral hepatitis. Table or Figure Upload"

Retrospective data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Infectious Disease • Inflammation • Rare Diseases

Gene-based therapies for hemophilia. (PubMed, Res Pract Thromb Haemost) - "Clinical outcomes have shown promise through gene therapies like valoctocogene roxaparvovec for hemophilia A and etranacogene dezaparvovec and fidanacogene elaparvovec for hemophilia B. Each therapy has demonstrated efficacy in reducing bleeding rates and maintaining factor activity. Current trials are exploring new vectors, transgenes, and methods to overcome existing limitations. Gene therapy holds the potential to revolutionize hemophilia treatment, offering a path toward long-term management and improved quality of life for patients."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

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

A Novel Agent-based Computational Model for Liver-targeting, AAV-based Gene Therapies Could Predict Response Durability in Hemophilia B Patients Treated with Etranacogene Dezaparvovec (ASGCT 2025) - P3 | "While the model was applied here in the context of treating hemophilia B, the modeling and simulation-based framework should be adaptable to many other AAV-based gene therapies. Disease Focus of Abstract:Hemophilia"

Clinical • Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

GENE THERAPY OF HEMOPHILIA B: IDENTIFICATION OF THE MOST EFFICIENT AAV SEROTYPE VECTOR FOR TRANSDUCTION OF HUMAN HEPATIC CELLS (ASGCT 2025) - "In 2022, the United States Food and Drug Administration (USFDA) approved Hemgenix, an AAV5-based vector from uniQure for gene therapy of hemophilia B. A relative high dose of 2x1013 vgs/kg of this vector leads to up to ~12% expression of the human clotting factor IX (hFIX)...All of these proof-of-concept studies make a compelling case for the use of AAV3 vectors with lower immunogenicity, improved safety, ensuring translation to the clinic with higher probability of success for gene therapy of hemophilia B. Furthermore, the reduced vector production costs as well as lower cost per patient should allow the eligible patient population worldwide to benefit from AAV3 vector-mediated gene therapy of hemophilia B in particular, and human liver diseases in general, in which other AAV serotype vectors have proven to be less than optimal. Disease Focus of Abstract:Hemophilia"

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Rare Diseases • MET

Do Breakthrough Therapies Demonstrate Breakthrough Value to Payers? An Evaluation of US Hemophilia B Gene Therapy Access Policies (ISPOR 2025) - " The study included two FDA-approved Hemophilia gene therapies: Hemgenix (22November2022) and Beqvez (25April2024)... US payer policies defined a narrow patient population for Hemophilia B gene therapies compared to product FDA labels, sometimes restricting eligibility beyond clinical trial criteria. This targeted review identified misalignment between payers and regulators on the clinical value of Hemophilia B Breakthroughs."

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases