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

Biphasic Transaminitis During Corticosteroid Tapering After Etranacogene Dezaparvovec Gene Therapy for Haemophilia B: Management Lessons From the First Spanish Case. (PubMed, Haemophilia) - No abstract available

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

Treatment With Etranacogene Dezaparvovec in a Renal Transplant Recipient With Hemophilia B on Concomitant Systemic Immunosuppressive Therapy. (PubMed, Haemophilia) - No abstract available

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

An AAV5-hFIX-Padua single dose study of 14 month-old NHP with 2 year LTFU supports dosing of HEMGENIX® in juvenile Hemophilia B patients (ESGCT 2026) - No abstract available

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

Bridging the Gap: A Systematic Review of Modern Hemophilia Therapies and Global Inequities in Clinical Trial Participation. (PubMed, Haemophilia) - "Modern therapies demonstrate strong efficacy and acceptable safety, with several approved agents. However, persistent global inequities in trial participation and access highlight the need for more inclusive research and equitable implementation strategies."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Long-term Follow-up Study of Male Adults With Hemophilia B Previously Treated With Etranacogene Dezaparvovec (CSL222) (clinicaltrials.gov) - P2/3 | N=56 | Enrolling by invitation | Sponsor: CSL Behring | Phase classification: P ➔ P2/3

Phase classification • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Efficacy and Safety of Adeno-associated Virus-Based Gene Therapies for Hemophilia B: a Systematic Review and Meta-Analysis (ISTH 2026) - "At 1 year, mean FIX:C was 55.84% (95%CI: 44.92- 66.75) for BBM-H901, higher than etranacogene dezaparvovec (41.32%, 95%CI: 36.08-46.57) and fidanacogene elaparvovec (28.93%, 95%CI: 23.66-34.20), with this trend persisting at 2 and 3 years (Figure 1). Table or Figure Upload (1) Figure 1. Efficacy outcomes: FIX:C at 1 (A), 2 (B), 3 (C) years, and change of ABR from baseline at 1 year (D) Page 2 DOI*10.1016/j.rpth.2026.104798"

Gene therapy • Retrospective data • Review • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Vulnerability, protection and fairness: ethical and regulatory limits in small-N gene therapy trials. (PubMed, Trials) - "Current gene therapy trial frameworks largely succeed in supporting methodological flexibility for ultra-rare conditions but insufficiently operationalize fair inclusion. Ethical concerns arise not because participant protections are excessive, but because the burdens associated with necessary scientific and regulatory requirements may disproportionately affect patients facing structural disadvantages. Ensuring justice in ultra-rare gene therapy research requires extending proportionate, risk-based approaches beyond evidence generation to include the identification and mitigation of foreseeable barriers to participation."

Journal • Gene Therapies • Rare Diseases

Etranacogene dezaparvovec in hemophilia B: early safety insights. (PubMed, Recenti Prog Med) - No abstract available

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

PRAC adopted a Type II variation for HEMGENIX to update the protocol and Statistical Analysis Plan (SAP) for the post-authorization observational study CSL222_4001, a Specific Obligation listed in Annex II. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 6 – 9 Jul 2026: The long-term follow-up study evaluates the effectiveness and safety of HEMGENIX in the commercial setting. Consequently, Annex II and RMP version 1.1 were updated accordingly. [AI generated summary]

PRAC • Hemophilia B

Presentation Theater 2 Visit the HEMGENIX® Presentation Theatre to learn more about advancing hemophilia B care with gene therapy (ISTH 2026) - "Sponsored by CSL"

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

Artificial Intelligence and Gene Therapy: about the first patient to receive Etranacogene Dezaparvovec (ED) in Spain (ISTH 2026) - "Constant updating is a guarantee of the quality of the answers. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) Page 3 DOI*10.1016/j.rpth.2026.105848"

Clinical • Gene therapy • Gene Therapies • Hematological Disorders

Preliminary Evidence of AAV5 Immunity in a Taiwanese Hemophilia B Cohort (ISTH 2026) - "While most trials exclude patients with NAbs, AAV5-based Etranacogene Dezaparvovec is an exception...However, interpretation is limited by small sample size; further studies are warranted. DOI*10.1016/j.rpth.2026.104802"

Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Rare Diseases

EARLY IMPACT OF GENE THERAPY (GT) ON JOINT HEALTH IN HEMOPHILIA B: AN N-OF-1 STUDY WITH COUNTERFACTUAL MODELING (ISTH 2026) - "GT with etranacogene dezaparvovec (ED) achieves sustained FIX expression and has demonstrated significant bleeding reduction in 5-year HOPE-B trial...Methods N-of-1 observational study in patient with established arthropathy (baseline HEAD-US=7), and prior prophylaxis with eftrenonacog alfa 60 IU/kg weekly (FIX trough 4–5%)...Bayesian modeling supports that GT could modify natural history of joint disease, not only bleeding. Table or Figure Upload (1) Figure 1 Page 2 Table or Figure Upload (2) Table 1 DOI*10.1016/j.rpth.2026.104792"

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

ALT Elevation and FIX Dynamics After Gene Therapy with Etranacogene Dezaparvovec: A Real-World Case from Spain (ISTH 2026) - "Results Our patient suffered 2 peaks in ALT: Week 4, first ALT elevation (51 IU/L, FIX 26, 9%, drop 20%) with fast response to Prednisone (ALT normal and increase in FIX). FIX expression remained >50% at all times. This supports the HOPE-B findings that ALT increases are not necessarily associated with loss of efficacy, but also highlights the need for individualized immunomodulatory tapering protocols and long-term biochemical follow-up beyond the early post- infusion window Table or Figure Upload (1) Table 1 Page 2 DOI*10.1016/j.rpth.2026.104801"

Clinical • Gene therapy • Real-world • Real-world evidence • Gene Therapies • Hepatology • Inflammation

SUSTAINED FIX RESPONSE AFTER ETRANACOGENE DEZAPARVOVEC: 7-MONTH FOLLOW-UP OF THE 1ST PATIENT TREATED IN SPAIN (ISTH 2026) - "Oral prednisone followed local protocol, EPAR Hemgenix and recently WFH 2025 guidelines. IS adapted to clinical and laboratory evolution. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.104799"

Clinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Bayesian Predictive Modeling of Long-Term FIX Durability in Real-World Etranacogene Dezaparvovec Treatment: First Spanish Experience with High-Density Monitoring (ISTH 2026) - "The workflow is reproducible and adaptable for other canters to generate patient-specific forecasts. Longitudinal follow-up will enable mixed/joint models (LMM/Cox) to refine durability predictions Table or Figure Upload (1) Table 1 Page 2 Table or Figure Upload (2) Table 2 Page 3 DOI*10.1016/j.rpth.2026.104797"

Clinical • Predictive model • Real-world • Real-world evidence • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Durable efficacy and safety in responders: 5-Year post hoc end-of-study analysis of etranacogene dezaparvovec in the phase 3 HOPE-B trial in patients with severe/moderately severe haemophilia B (ISTH 2026) - P3 | "Page 2 Table or Figure Upload (1) Figure 1. Adjusted ABRs during lead-in a versus Months 7–60 (n=52) DOI*10.1016/j.rpth.2026.103567"

Clinical • P3 data • Retrospective data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

HEMGENIX® in Practice: Real-World Strategies and Learnings (ISTH 2026) - No abstract available

Clinical • Real-world • Real-world evidence

CSL Canada Announces First Canadian Patient Receives HEMGENIX (etranacogene dezaparvovec) Hemophilia B Gene Therapy in Ontario, Canada (Canada Newswire) - "CSL Canada is proud to recognize this important milestone of the first Canadian patient to receive HEMGENIX (etranacogene dezaparvovec), the one-time gene therapy treatment for eligible patients living with hemophilia B, at London Health Sciences Centre in London, Ontario."

Launch Canada • Hemophilia B

Assessment of Evolution in FDA’s Regulatory Perspectives on Gene Therapy Studies for Benign Hematologic Conditions (ASGCT 2026) - "Methods FDA’s publicly available BLA review memos were evaluated to look for changes in FDA’s perspectives during the interval of time between the licensures for etranacogene dezaparvovec-drlb (2022) and fidanacogene elaparvovec-dzkt (2024). Overall, FDA’s regulatory considerations for the clinical reviews of the two BLAs appeared to be highly concordant, which has not always been the case for multiple gene therapies approved by FDA for a given indication. This demonstrates strong conviction by FDA in its regulatory paradigm for approval of hemophilia B gene therapy products and provides a clear roadmap for future development programs in this area."

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

What is the formula for commercial success of a gene therapy? Reflections on approved GTx (ASGCT 2026) - "Indication selection: Commercial success across Casgevy®, Vyjuvek®, Elevidys® and Zolgensma® reinforce five criteria that appear pivotal for gene therapy success...Beqvez® (hemophilia B) appears to have treated no patients between FDA approval (2024) and market withdrawal (2025), while Hemgenix® treated 12 patients in its first year (<0.1% penetration). Uptake has also remained minimal for Zevaskyn® and Zynteglo® (beta-thalassemia).By contrast, Elevidys® (DMD) treated approximately 900 patients in the US within two years of FDA approval, although it did not receive EU authorization... The number of clinical study initiations increased continuously over the observation period, rising by 430% from 27 ongoing company sponsored programs in 2016 to 143 in 2025. After steady growth until 2021, development activity accelerated markedly from 2022 onward, with the pipeline almost doubling between 2022 and 2023. After a peak in 2024,..."

Gene therapy • Beta-Thalassemia • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Ophthalmology • Rare Diseases

Review of Viral Shedding Profiles in Approved AAV-Based Gene Therapy Products: Implications for Safety and Environmental Impact (ASGCT 2026) - "The GTPs were categorized based on their route of administration: locally administered (Luxturna, Upstaza, Glybera, Adstiladrin) and systemically administered (Beqvez, Roctavian, Hemgenix, Elevidys, Zolgensma)...Given that AAV is non-pathogenic to humans, it is feasible to standardize and simplify viral shedding monitoring in clinical studies. The standardization could streamline sampling schedules, reducing the burden on patients while still generating sufficient data to address potential transmission and environmental risks in compliance with regulatory requirements."

Clinical • Gene therapy • Review • Duchenne Muscular Dystrophy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Development of RGD-Free AAV Capsid with Myocytes Tropism and Non-Liver Targeting by Directed Evolution in Non-Human Primates (ASGCT 2026) - "So far, FDA proved several wild-type AAV (wtAAV) serotypes-based gene therapies for rare diseases by intravenous (IV) administration such as AAV5, AAV9 and AAVrh74 in the products of Hemgenix, Zolgensma and Elevidys, respectively...In the translational study and head-to-head comparation, ID-31 delivered SERCA2a dramatically increased the gene-of- interest (GOI) expression in heart and decreased the GOI level in liver compared with the state-of-the-art AAV1-SERCA2a therapy in many clinical trials in NHP...B) the DNA level in heart, muscle and liver. C) the transcription efficiency in each organs."

Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Infectious Disease • Rare Diseases • FGF21 • MB

Gene Therapy in Hemophilia: Clinical Advances, Immunological Challenges, and Emerging Therapeutic Perspectives. (PubMed, Int J Mol Sci) - "In aggregate, these perspectives position gene therapy not as a singular curative event but as a component of an evolving, biologically integrated management strategy. Long-term follow-up translational research (LTFU) and coordinated global efforts will be essential to optimize durability, safety, and equitable access."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Immune Modulation • Immunology • Rare Diseases