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

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

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

Population Modeling of Factor IX Activity Following Administration of Fidanacogene Elaparvovec Gene Therapy in Participants with Hemophilia B. (PubMed, Clin Pharmacokinet) - P2, P3 | "Model-based estimates showed that a single dose of fidanacogene elaparvovec elicited long-lasting elevations in FIX activity, suggesting most individuals would not require prophylactic FIX replacement for at least 15 years post-infusion."

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

Wolfgang Miesbach: Six-Year Gene Therapy Data for Haemophilia B at ISTH2025 (OncoDaily) - P1/2 | N=15 | NCT02484092 | Sponsor: Pfizer | "'The remarkable long-term data from the phase 1/2a highlight the durability and safety of a single 5 × 10¹¹ vg/kg infusion of fidanacogene elaparvovec in 14 adults with haemophilia B (mean age 40.1 y; 14.3% HIV+)...Efficacy at 6 years: FIX activity held steady in the mild range (mean 22.3 – 26.1%); 13/14 participants (93%) stayed in the mild range throughout follow-up; Zero bleeds in the majority (71 %) of participants; No one resumed prophylaxis during the entire 6-year period; Annualized bleeding rate remained < 1 from year 1 through year 6...Safety profile: No treatment-related adverse events after year 1; 5/14 had liver ultrasound findings deemed pre-existing or unrelated (steatosis, gallstones, cirrhosis progression); No thrombotic events, malignancies, or FIX inhibitors detected at any point.'"

P1/2 data • Hemophilia B

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=51 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Feb 2031 ➔ Feb 2028

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

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

Multi-Year Follow-Up of Fidanacogene Elaparvovec for Moderately Severe/Severe Hemophilia B (ISTH 2025) - P3 | "No treatment-related SAEs were reported beyond Yr 1. Table or Figure Upload"

Gene Therapies • Hemophilia • Hemophilia B • Oncology • Rare Diseases

A phase 2 dose-escalation substudy of fidanacogene elaparvovec in adults with hemophilia B (ISTH 2025) - "The most frequently reported TRAE (Table 1) was increased alanine aminotransferase (ALT); all increases were managed with increasing doses of CS administered orally (1 pt in cohort 2 also received mycophenolate mofetil post CS) and all AEs were resolved by the cutoff date. One pt (cohort 2; history of cranial hemorrhage) resumed preventative prophylaxis on Day 351 based on their FIX levels. Table or Figure Upload"

Clinical • P2 data • Gene Therapies • Hemophilia • Hemophilia B • Rare Diseases

Six-year outcomes following fidanacogene elaparvovec in adults with hemophilia B (ISTH 2025) - P2 | "No pts resumed FIX prophylaxis. Table or Figure Upload"

Clinical • Gene Therapies • Hemophilia • Hemophilia B • Oncology • 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

Deconstructing FDA's Expedited Program Determinations: Analyzing how the Agency may Set the Bar for RMAT Designation (ASGCT 2025) - "Parexel explored the relationship between the early-phase data from press releases around the time of RMAT designation and pivotal data from FDA review memos for marketing applications for two cases of RMAT-designated gene therapies, VYJUVEK (beremagene geperpavec) and BEQVEZ (fidanacogene elaparvovec-dzkt), that were approved in 2023 and 2024. Conducting analyses, such as the one listed above, that contextualize the RMAT-designation supporting data within the totality of publicly disclosed information for that development program, can help inform developers in making decisions about the amount of evidence and timing for submission of RMAT designation requests. Disease Focus of Abstract:Other Other: Rare Disease"

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

Fidanacogene Elaparvovec for Hemophilia B - A Multiyear Follow-up Study. (PubMed, N Engl J Med) - P2 | "Fidanacogene elaparvovec was associated with no or only low-grade adverse effects over a period of 3 to 6 years. Efficacy was maintained in the long term at 5×1011 vg per kilogram, one of the lowest intravenous doses of AAV used for any indication. (Funded by Pfizer; ClinicalTrials.gov number, NCT03307980.)."

Journal • Fibrosis • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Oncology • Rare Diseases

Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec in Patients With Hemophilia A or B Respectively (clinicaltrials.gov) - P3 | N=263 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2039 ➔ Feb 2040 | Trial primary completion date: Sep 2039 ➔ Feb 2040

Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Pfizer discontinues hemophilia treatment Beqvez, emptying its gene therapy portfolio (Fierce Pharma) - "The New York pharma is ending global development and commercialization of Beqvez less than a year after an FDA approval for the gene therapy to treat hemophilia B...Several reasons led to the discontinuation, including limited interest from patients and doctors toward hemophilia gene therapies to date, a Pfizer spokesperson told Fierce Pharma in a statement....No patients seem to have received commercial Beqvez since its FDA nod in April 2024. The Pfizer spokesperson said the company will communicate the news to patients and providers that are in the treatment qualification process, adding that the company remains committed to supporting those who received the med in any clinical trial."

Discontinued • Hemophilia B

Gene-ius at work: Hemophilia B treatment enters a new era. (PubMed, Am J Health Syst Pharm) - "For the first time in history, individuals with hemophilia B have access to potentially curative therapies through gene therapy. Both etranacogene dezaparvovec and fidanacogene elaparvovec offer significant efficacy, reducing the number of bleeding episodes and raising FIX concentrations with a single lifetime administration. While concerns remain regarding long-term safety and durability, these therapies represent a major advancement in reducing treatment burden and improving quality of life for patients. The future of hemophilia B management now holds the promise of greater independence from frequent prophylactic treatments."

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