Beqvez (fidanacogene elaparvovec-dzkt) / Roche, Pfizer - LARVOL DELTA

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

C0371003: Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B (clinicaltrials.gov) - P2 | N=21 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed | Trial completion date: Oct 2029 ➔ Jul 2026 | Trial primary completion date: May 2029 ➔ Jul 2026

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

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

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

Overview of Patient-Reported Outcomes in Haemophilia Gene Therapy. (PubMed, Transfus Med Hemother) - "In the SPK-9001 long-term follow-up, durable Haem-A-QoL gains were confirmed through 156 weeks...These PRO-derived improvements are also the principal driver of gene therapy's economic value since cost-effectiveness models show substantial gains in health-related quality of life but negligible gains in life expectancy. Priorities include standardised coreHEM measurement, long-term registries, and ensuring certified haemophilia centres are equipped for systematic PRO follow-up."

Journal • Review • Gene Therapies • Hematological Disorders • Hemophilia • Mood Disorders • Psychiatry • Rare Diseases

A case of phenotoxicity after fidanacogene elaparvovec: supratherapeutic FIX and multiple thromboembolisms after AAV gene therapy for haemophilia B (ISTH 2026) - "A local standard operating procedure has been developed to provide guidance on the detection and management of phenotoxicity in patients who have received gene therapy for haemophilia and a prototype medical alert card has been developed as a tool to improve communication with external healthcare professionals providing emergency care to gene therapy patients. Conclusions This case highlights the challenges of long-term monitoring, detection and management of phenotoxicity following AAV gene therapy for haemophilia B. DOI*10.1016/j.rpth.2026.104795"

Clinical • Gene therapy • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Pulmonary Disease • Pulmonary Embolism • Rare Diseases • Thrombosis

C0371017: A Non-Investigational Product, Multi-Center Cohort Study to Describe Long-Term Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec (clinicaltrialsregister.eu) - P2/3 | N=31 | Not yet recruiting | Sponsor: Pfizer Inc.

New P2/3 trial • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

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

COMPARATIVE ANALYSIS OF GENE THERAPIES AUTHORIZED BY THE U.S. FOOD AND DRUG ADMINISTRATION AND THE EUROPEAN MEDICINES AGENCY (ISPOR 2026) - "Fidanacogene elaparvovec was discontinued from the market... The majority of gene therapies were authorized by both agencies, with the FDA approving products earlier than the EMA by a median of less than one year. Most therapies targeted rare diseases and received expedite development and approval procedures. There were differences in the indications of gene therapies authorized by FDA and EMA."

Gene therapy • Gene Therapies • Metabolic Disorders • Rare Diseases

C0371017: A Non-Investigational Product, Multi-Center Cohort Study to Describe Long-Term Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec (clinicaltrialsregister.eu) - P2/3 | N=29 | Not yet recruiting | Sponsor: Pfizer Inc.

New P2/3 trial • Hematological Disorders • Hemophilia • Hemophilia A • 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

C0371003: Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Jun 2029 ➔ Oct 2029

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

Safety, efficacy and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B. (PubMed, Blood Adv) - P2 | "Overall, fidanacogene elaparvovec exhibited a favorable safety profile, sustained efficacy, and improved PROs for up to 6 years. This trial is registered at www.clinicaltrials.gov as #NCT03307980."

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

Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec in Patients With Hemophilia A or B Respectively (clinicaltrials.gov) - P3 | N=173 | Recruiting | Sponsor: Pfizer | N=263 ➔ 173

Enrollment change • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

30 years of classical hematology drugs in the US: Approvals, costs, and sales (ASH 2025) - "Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban(2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec(2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor(2019/2024/safety).There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulantsin atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists)...Classical hematology drugs contribute substantially to US prescription drug spending, with over $70billion in annual sales and medications for thromboembolism accounting for over half of the costs.Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilarsnow represent two-thirds of approvals. Continuous-duration treatments, particularly for..."

Anemia • Atrial Fibrillation • Beta-Thalassemia • Cardiovascular • Chemotherapy-Induced Neutropenia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hemophilia • Immune Thrombocytopenic Purpura • Immunology • Myelodysplastic Syndrome • Nephrology • Neutropenia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Sickle Cell Disease • Thrombocytopenia • Thrombocytopenic Purpura

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

Impact of Fidanacogene Elaparvovec Gene Therapy on Joint Health in Adults With Haemophilia B: Results From a Phase 3 Study. (PubMed, Haemophilia) - No abstract available

Journal • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Characterizing a Cohort of Patients with Hemophilia B Treated with Fidanacogene Elaparvovec from the Phase 3 Benegene-2 Study Who Returned to Factor IX Prophylaxis (ASH 2023) - P3 | "The 6 RTP participants who received fidanacogene elaparvovec in the phase 3 study (BENEGENE-2) initially responded to therapy before a heterogenous decline in FIX activity. The limited number of participants and lack of consistent patterns and demographic features make identifying predictors of potential RTP challenging. Although all RTP participants were treated with corticosteroids during this study, not all participants treated with corticosteroids RTP of FIX."

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

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

Fidanacogene Elaparvovec-dzkt for Treatment of Adults with Moderate to Severe Hemophilia B (ASH 2024) - No abstract available

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

Health-Related Quality of Life in Adults with Hemophilia B after Receiving Gene Therapy with Fidanacogene Elaparvovec (ASH 2023) - P2 | "HRQoL improvements after gene therapy are an indicator that fidanacogene elaparvovec can reduce the burden associated with hemophilia. PRO assessments will be a part of BENEGENE-2, an ongoing pivotal phase 3 study to demonstrate the efficacy of fidanacogene elaparvovec and will provide additional insights via the analyses of secondary endpoints into HRQoL benefits for participants with HB following gene therapy with fidanacogene elaparvovec."

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

Use of Fidanacogene Elaparvovec, a Gene Therapy Vector, to Deliver a Stable, Fully Functional Human Factor IX Transgene for the Treatment of Hemophilia B: A Combined Analysis of Safety (ASH 2024) - P2, P3 | "Conclusions This combined analysis demonstrates the favorable safety profile of fidanacogene elaparvovec in the largest dataset with the longest follow-up for an HB gene therapy. LTFU will continue for up to 15 years."

Clinical • Gene therapy • Anemia • Fibrosis • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Nephrology • Oncology • Polycystic Kidney Disease • Rare Diseases • Renal Disease

Health-related quality of life in adults with hemophilia B after gene therapy with fidanacogene elaparvovec: Results from the BENEGENE-2 trial. (PubMed, J Thromb Haemost) - "Fidanacogene elaparvovec improved health-related quality of life and health and functional status in adults with hemophilia B."

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

BENEGENE-2: A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P3 | N=72 | Active, not recruiting | Sponsor: Pfizer | N=51 ➔ 72 | Trial completion date: Feb 2028 ➔ Feb 2031

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