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

Karmanos Cancer Institute Becomes First and Only Free-Standing Cancer Center to Treat Hemophilia B with New Gene Therapy (PRNewswire)

Commercial • Hemophilia B

CSL's hemophilia B gene therapy HEMGENIX recommended for reimbursement in Norway, a key step for European rollout. (AD HOC NEWS)

Reimbursement • Hemophilia B

CSL is currently experiencing a temporary global stockout of HEMGENIX that will result in delays in treatment for some individuals in countries with established commercial access. (CSL Behring Press Release) - "We want to be very clear that this situation is not related to the safety or effectiveness of HEMGENIX. Rather, it reflects the complexity of manufacturing gene therapies, and our commitment to adhering to the highest regulatory and quality standards for the people we serve. We are working with regulatory authorities on strategies to ensure stable ongoing supply for HEMGENIX while preserving our high-quality standards."

Commercial • Hemophilia B

A NOVEL BAYESIAN MODELING APPROACH INCREASES PRECISION OF PREDICTED LONG-TERM DURABILITY OF ETRANACOGENE DEZAPARVOVEC FOR THE TREATMENT OF HEMOPHILIA B (ISPOR 2026) - "The BASE model generated statistically unbiased estimates and was validated through comparison with observed findings. The predictive results reduce the uncertainty around the long-term durability of etranacogene dezaparvovec suggesting that there is sustained durability anticipated for > 90% of patients over a period of 25 years."

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

SUSTAINED FACTOR IX LEVELS AT 5-YEARS AFTER ETRANACOGENE DEZAPARVOVEC - THE EXPONENTIAL DECAY MODEL MAY UNDERESTIMATE OBSERVED RESULTS (ISPOR 2026) - "Although the exponential decay assumption appeared to align with the 2-year HOPE-B FIX trend, it may not have fully captured the plateau observed in longer-term (5-year) results. Including the 5-year data did not improve predictions suggesting the exponential decay model doesn't accurately represent the observed FIX trajectory and may underestimate the gene therapy durability. Using non-linear modelling methods which reflect the more recent clinical data may increase confidence in the durability of gene therapy."

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

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

Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial. (PubMed, Res Pract Thromb Haemost) - "No late hepatotoxicity was observed. Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population."

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

Etranacogene dezaparvovec in people with hemophilia B and without adeno-associated virus serotype 5 neutralizing antibodies: a 4-year subgroup analysis of the Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) trial. (PubMed, Res Pract Thromb Haemost) - "No treatment-related oncogenic events or persistent late hepatotoxicity were observed. Etranacogene dezaparvovec proved to be highly effective, superior to FIX prophylaxis for bleeding protection, and safe for 4 years postinfusion in NAb- persons with severe or moderately severe hemophilia B."

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

Balancing Promise and Peril: Hemophilia Gene Therapy Insights. (PubMed, IUBMB Life) - "Over the past three decades, remarkable advancements have been made in hemophilia gene therapy, culminating in the approval of Valoctocogene roxaparvovec (ROCTAVIAN, AAV-FVIII) and Etranacogene dezaparvovec (HEMGENIX, AAV-FIX) for patients with severe HA and HB, respectively. Nevertheless, gene therapy poses questions regarding its long-term efficacy and safety. This review synthesizes findings from clinical trials, addresses persistent challenges in hemophilia gene therapy, and underscores the biological constraints and limitations inherent to viral vector-based approaches."

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

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

Overview of gene therapy for hemophilia: questions and answers to navigate the innovation. (PubMed, J Thromb Haemost) - "Recent phase III trials of valoctocogene roxaparvovec (hemophilia A) and etranacogene dezaparvovec (hemophilia B) have shown durable factor expression for up to 5 years, with the Factor IX-Padua variant enhancing treatment efficacy 5-8 fold. While challenges remain regarding long-term durability, immune responses, and standardized care pathways, current AAV-based therapies represent a transformative advance. Future developments including alternative vectors, enhanced factor variants, and gene editing technologies promise to further improve treatment outcomes and expand patient access."

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

Etranacogene dezaparvovec in haemophilia b: Report of 1ST patient receiving HEMGENIX® in Spain (ASH 2025) - "RESULTS A 41-year-old male with moderately severe HB (baseline FIX 1.8%) was on prophylaxis with eftrenonacog alfa (50 IU/kg weekly)...In our case, the patient's evolution follows the expected pattern: good initial response, mild and reversible liver enzyme elevation with use of prednisone, and satisfactory FIX levels. Immunosuppression is being adapted to clinical and laboratory evolution. We expect to present updated 6-month data at the ASH 2025 Congress."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis C • Infectious Disease • Rare Diseases • Rheumatology

Elevation of liver health biomarkers before and after etranacogene dezaparvovec gene therapy in hemophilia B: Associations with long-term clinical outcomes (ASH 2025) - P3 | "Although theone participant without baseline ALT elevation had a history of HIV, HBV, and HCV, the late ALT elevationwas assessed by the investigator as alcohol related. Late increases in ALT did not affect FIX activity inthese participants.Treatment-related transaminitis following M6 occurred in only one participant (ALT 1.2 ULN) at a singletimepoint in Y4, which resolved without sequelae.ConclusionFollowing a single dose of etranacogene dezaparvovec, participants with pre-dose elevated ALT/AST orpost-dose (CS-treated) ALT elevation maintained FIX expression (albeit lower in the ALT/CS group) andhad similar bleed reduction up to 4 years post-dose, compared to those without ALT elevations.Long-term liver deterioration following liver-targeted gene therapy was not observed over four years, noteven in those identified as potentially at risk due to subacute liver inflammation following vector delivery.These findings demonstrate that in cases of mild ALT/AST elevation..."

Biomarker • Clinical • Clinical data • Gene therapy • Fibrosis • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Rare Diseases

End-of-study analysis of the HOPE-B trial confirms the durable efficacy and safety of etranacogene dezaparvovec hemophilia b gene therapy over 5 years (ASH 2025) - P3 | "The completed 5-year HOPE-B trial conclusively demonstrated that a single dose ofetranacogene dezaparvovec delivers sustained, robust, endogenous FIX Padua expression, significantlyreducing bleeding rates and the need for exogenous hemostatic support in most participants with severeor moderately severe hemophilia B. This gene therapy showed a favorable safety profile, with no late-onset AAV-related oncogenicity or hepatotoxicity observed. The positive benefit/risk ratio reported herehighlights etranacogene dezaparvovec as a transformative therapy for individuals with hemophilia B.Consenting HOPE-B participants will be monitored long-term until 15 years post-treatment in the IX-TEND3003 study."

Clinical • Gene therapy • Brain Cancer • CNS Tumor • Gene Therapies • Hematological Disorders • Hematological Malignancies • Hemophilia • Hemophilia B • Hepatocellular Cancer • Myelodysplastic Syndrome • Rare Diseases • Solid Tumor

Liver dysfunction in AAV-mediated Hemophilia B gene therapy: Mechanisms and management strategies. (PubMed, Blood Rev) - "Clinical trials involving Etranacogene Dezaparvovec, Fidanacogene Elaparvovec, and BBM-H901 (Dalnacogene Ponparvovec) reported transient elevations in liver enzymes, typically occurring 2-6 weeks post-infusion. The hepatic complications, while manageable, pose a risk to therapeutic efficacy and highlight the need for careful monitoring, early detection, and personalized immunosuppressive strategies. This review explores the mechanisms of AAV-induced liver dysfunction in gene therapy for Hemophilia B, with a focus on clinical manifestations, immune-mediated pathogenesis, and emerging approaches for mitigating liver-related adverse effects and providing clinical guidance."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Liver Failure • Rare Diseases

Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B. (PubMed, N Engl J Med) - P3 | "Sustained endogenous factor IX expression and low annualized bleeding rates over a 5-year period were observed after an infusion of etranacogene dezaparvovec. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.)."

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

Data Published in the New England Journal of Medicine Confirm the Long-term Durability and Safety of HEMGENIX (etranacogene dezaparvovec-drlb) Over Five Years (PRNewswire) - "The five-year follow-up analysis demonstrated: Durable Factor IX Activity: Mean factor IX activity levels were sustained at greater than 36% during years one through five post-infusion: mean factor IX levels of 41.5 IU/dL (n=50) at year one, 36.7 IU/dL (n=50) at year two, 38.6 IU/dL (n=48) at year three, 37.4 IU/dL (n=47) at year four, and 36.1 IU/dL (n=48) at year five. Sustained Bleed Protection: The mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from the lead-in (4.16, n=54) compared to year five (0.40, n=51) post-infusion."

P3 data • Hemophilia B

Deconstructing gene therapy in hemophilia for the clinician. (PubMed, Hematology Am Soc Hematol Educ Program) - "After decades of research, gene therapy for hemophilia is now commercially available for both hemophilia A and B. Currently, two products, valoctocogene roxaparvovec (for hemophilia A) and etranacogene dezaparvovec (for hemophilia B), have been licensed following approval in the United States and several other countries. This review's aims are (1) to deconstruct gene therapy in hemophilia and provide a basic framework for understanding its components and processes, including the transgene, the vector, and the delivery systems, in order to help clinicians present gene therapy as a treatment option in a shared decision-making model, better understand the clinical data, and explain gene therapy to their patients; (2) to gain knowledge of the currently approved gene therapies for hemophilia A and B, including their eligibility and exclusion criteria and the range of expected outcomes; and (3) to comprehend the shared decision-making process for these therapies and their..."

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

Long-term durability of rAAV gene therapy in hemophilia: Factor expression, clinical outcomes and underlying molecular mechanisms. (PubMed, Blood Rev) - "Approved therapies-valoctocogene roxaparvovec for hemophilia A and etranacogene dezaparvovec for hemophilia B-have demonstrated significant reductions in bleeding frequency and factor replacement requirements. Emerging strategies to enhance durability include next-generation vector design, codon optimization, gene editing technologies, and alternative delivery platforms. This review synthesizes current clinical evidence, biological understanding, and translational challenges, with an emphasis on strategies to optimize long-term efficacy of AAV-mediated gene therapy for hemophilia."

Clinical data • Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

First Real-World Experience Administering Etranacogene Dezaparvovec Gene Therapy for People with Hemophilia B (ASH 2023) - "By implementing early and iterative education and developing center-specific protocols, the Hemophilia Outreach Center was able to successfully administer etranacogene dezaparvovec-drlb. These elements are crucial to ensure smooth execution and optimal patient outcomes."

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

Long-Term Bleeding Protection, Sustained FIX Activity, Reduction of FIX Consumption and Safety of Hemophilia B Gene Therapy: Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec in Adult Patients with Severe or Moderately Severe Hemophilia B (ASH 2023) - P3 | "Long-term follow-up during the HOPE-B trial has shown that a single-dose of etranacogene dezaparvovec resulted in long-term endogenous FIX Padua expression and superior bleeding protection compared to FIX prophylaxis in participants without or with AAV NAb titer ≤1:678, with a favorable safety profile over 3 years post-administration."

Clinical • Gene therapy • Cardiovascular • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatocellular Cancer • Oncology • Rare Diseases • Solid Tumor

Role of Pharmacy Professionals in Gene Therapy Based on Adeno-Associated Viruses: Treatment of Hemophilia as a Template of Care. (PubMed, Can J Hosp Pharm) - "Recently approved AAV-based treatments for hemophilia, such as etranacogene dezaparvovec and fidanacogene elaparvovec, could provide long-term benefits by targeting the genetic basis of the condition. Furthermore, pharmacy professionals can help address challenges such as financial obstacles, regulatory adherence, and ethical issues. Using their expertise in medication management, patient education, and health system processes, pharmacy professionals can enhance the safety, effectiveness, and accessibility of AAV-based gene therapies for hemophilia, ultimately leading to better patient outcomes."

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

In Vitro and In Vivo Potency Differences between AAVRh74var and AAV5 Vectors Encoding the Same High-Activity Human Factor IX Variant, FIX-R338L, Expression Cassette: Implications for Hemophilia B Gene Therapy (ASH 2024) - "The only other approved HB gene therapy (etranacogene dezaparvovec) utilizes the AAV5 capsid and is administered at a 40-fold higher dose (2×1013 gc/kg). Overall, the results demonstrate differences between the AAVRh74var and AAV5 capsids. This is consistent with fidanacogene elaparvovec (AAVRh74var) achieving clinically robust efficacy, despite a several-fold lower dose than AAV5-based gene therapies."

Gene therapy • Preclinical • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatocellular Cancer • Oncology • Rare Diseases • Solid Tumor

Development of an Ex Vivo Precision Gene Engineered B Cell Medicine That Produces Active and Sustained Levels of FIX for the Treatment of Hemophilia B (ASH 2023) - "More recently, an adeno-associated virus (AAV) vector-based gene therapy, etranacogene dezaparvovec, has been approved for some adults as a potential new option...The qPCR data confirms the expected biodistribution of FIX-expressing BeCMs, which engraft and persist in bone marrow tissue over time. In summary, we have developed an ex vivo precision gene engineered B cell medicine that produces active and sustained levels of FIX for the treatment of hemophilia B. The potential therapeutic application of this unique biologic delivery system could afford a novel treatment modality for hemophilia B."

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

Adult Patients with Hemophilia B and with a History of Chronic HCV/HBV Infection Receiving Liver-Directed Gene Therapy Demonstrated Long-Term Bleeding Protection and Sustained FIX Activity: Efficacy and Safety Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec (ASH 2023) - P2 | "The majority of HOPE-B trial participants were adults with a history of chronic HCV and/or HBV infection without active viral disease or evident pre-existing liver fibrosis. Safety and efficacy are observed in the HCBV participants."

Clinical • Gene therapy • Fibrosis • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Oncology • Rare Diseases • Solid Tumor • AFP • CD4