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

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: Apr 2038 ➔ Sep 2039 | Trial primary completion date: Apr 2038 ➔ Sep 2039

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

Beqvez - another gene therapy for hemophilia B. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Efficacy and safety of fidanacogene elaparvovec in adults with moderately severe or severe hemophilia B: updated results from the phase 3 BENEGENE-2 gene therapy trial (ISTH 2024) - P3 | "Forty-five participants (median [range] age, 29 [18–62] years) were dosed with fidanacogene elaparvovec 5e11 vg/kg. As of August 2023, 44 participants completed ≥15 months follow-up (up to 4.0 years); the 45th participant had >12 months follow-up; we previously reported on 41 with ≥15 months of follow-up). Total ABR was reduced by 71% from Week 12 to Month 15 post-gene therapy vs prophylaxis (mean ABR, 1.3 vs 4.4; P< 0.0001; Table 1)."

Clinical • Gene therapy • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec. (PubMed, Thromb Haemost) - P2 | " These results demonstrate FIX-R338L activity can be measured with OS and CS assays in clinical laboratories and provide insight into assay variability when measuring FIX with endogenously produced FIX-R338L. The findings may help establish best practices for measuring FIX-R338L activity (Clinicaltrials.gov identifier: NCT02484092)."

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

U.S. FDA Approves Pfizer’s BEQVEZ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B (Pfizer Press Release) - "Pfizer Inc...announced today that the U.S. Food and Drug Administration (FDA) has approved BEQVEZ (fidanacogene elaparvovec-dzkt) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test. BEQVEZ is a one-time treatment that is designed to enable people living with hemophilia B to produce FIX themselves rather than the current standard of care, which requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month."

BLA • Gene Therapies • Genetic Disorders • Hemophilia

Prediction of Long-Term Factor IX Durability Among Hemophilia B Patients Treated with Fidanacogene Elaparvovec Gene Therapy (ISPOR 2024) - P2, P3 | "Our model predicts that a vast majority of hemophilia B patients receiving fidanacogene elaparvovec would experience sustained long-term effects, maintaining FIX activity levels above 2% for up to 30 years after infusion."

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

LONG-TERM EVALUATION OF LIVER HEALTH IN PARTICIPANTS WHO RECEIVED FIDANACOGENE ELAPARVOVEC: DATA FROM A PHASE 1/2A STUDY WITH UP TO 6 YEARS OF FOLLOW UP (THSNA 2024) - P2, P3 | "Fidanacogene elaparvovec was generally well tolerated in HB participants on these studies. Long-term follow-up (up to 6 years) suggests stable long-term liver health. The finding of hepatic steatosis was unexpected and relationship to treatment is not known at this time."

P1/2 data • Gene Therapies • Hematological Disorders • Hemophilia • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Rare Diseases • AFP

A MULTI-YEAR FOLLOW-UP STUDY OF FIDANACOGENE ELAPARVOVEC GENE THERAPY FOR HEMOPHILIA B (THSNA 2024) - P2 | "Fidanacogene elaparvovec demonstrated long-term efficacy and was well tolerated over 3–6 years, reflecting the longest follow-up of participants with hemophilia B in a gene therapy trial. A phase 3 study is ongoing to further investigate these findings."

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Oncology • Rare Diseases • Rheumatology

Improved joint health after gene therapy with fidanacogene elaparvovec in people with hemophilia B: results from the BENEGENE-2 trial (WFH 2024) - No abstract available

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

Clinical efficacy of interventions for adult patients with moderately severe to severe hemophilia B: An indirect treatment comparison with fidanacogene elaparvovec (WFH 2024) - No abstract available

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Clinical efficacy of interventions for adult patients with moderately severe to severe hemophilia B: An indirect treatment comparison with fidanacogene elaparvoved (WFH 2024) - No abstract available

Clinical • Hematological Disorders • Hemophilia • 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=51 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2030 ➔ Jul 2030

Enrollment closed • Gene therapy • Trial completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Fidanacogene Elaparvovec: First Approval. (PubMed, Drugs) - "Fidanacogene elaparvovec is under regulatory review in the USA and the European Union and clinical studies are ongoing in multiple countries. This article summarizes the milestones in the development of fidanacogene elaparvovec leading to this first approval for moderately severe to severe (factor IX activity ≤ 2%) haemophilia B who are negative for neutralizing antibodies to AAVRh74var."

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

Simulation of Extended Half-Life Replacement FIX Therapy Dosing to Achieve Comparable FIX activity to that of Fidanacogene Elaparvovec Gene Therapy in Haemophilia B Patients (EAHAD 2024) - No abstract available

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

Efficacy and safety of fidanacogene elaparvovec in adults With moderately severe or severe hemophilia B: Updated results from the phase 3 BENEGENE-2 gene therapy trial (EAHAD 2024) - No abstract available

Clinical • Gene therapy • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Vector Clearance Following Administration of Fidanacogene Elaparvovec Gene Therapy in Adults With Hemophilia B (EAHAD 2024) - No abstract available

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

Health-related Quality of Life in Adults With Hemophilia B After Gene Therapy With Fidanacogene Elaparvovec in the BENEGENE-2 Trial (EAHAD 2024) - No abstract available

Clinical • Gene therapy • HEOR • Gene Therapies • Hematological Disorders • Hemophilia • 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 • 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 • Pain • 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 | Phase classification: P=N/A ➔ P3

Phase classification • Hematological Disorders • Hemophilia • Rare Diseases

"هيموفيليا (ب): مرض جيني نادر ينتج عن غياب عامل التجلط التاسع، مما يؤدي إلى زيادة سيولة الدم والنزيف 🗞فايزر @pfizer سلمت هيئة الغذاء والدواء @US_FDA طلب اعتماد للدواء التجريبي الجيني 💉🧬Fidanacogene elaparvovec لعلاج الهيموفيليا (ب) https://t.co/hxVuSlHNEL 1️⃣0️⃣" (@YAYshamsaldeen)

Efficacy and Safety of Fidanacogene Elaparvovec in Adults with Moderately Severe or Severe Hemophilia B: Results from the Phase 3 BENEGENE-2 Gene Therapy Trial (ISTH 2023) - P3 | "Forty-five participants (median [range] age, 29 [18, 62] years) were dosed with fidanacogene elaparvovec. Total ABR was reduced by 71% post-fidanacogene elaparvovec treatment vs prophylaxis (mean ABR, 1.3 vs 4.4; P< 0.0001; Table 1) and was stable over time (0.4 at Year 3; n=21). Mean FIX activity, measured by one-stage SynthASil, one-stage Actin-FSL, and chromogenic assays, is shown in Table 2."

Clinical • Gene therapy • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Impact of One-Stage Clotting Assay Reagents on Factor XIa Levels and Clotting Time with High Activity Factor IX (R338L) Variant (ISTH 2023) - "Background: Fidanacogene elaparvovec, a recombinant Adeno-associated virus vector encoding the human Factor IX-R338L high activity variant, is in development for Hemophilia B (HB)... Differences in FXIa, FIXa, FXa generation between the ellagic-acid and silica-based OS reagents were observed. In SynthASil, FXIa generation pre-calcification, and FIXa and FXa generation (20 and 40 seconds) post-calcification were lower compared to the ellagic acid reagents. Consistent with the variant's increased specific activity, FIXa and FXa were ~ 10 and 2-3-fold > FIX-WT, respectively."

Hematological Disorders • Hemophilia • Rare Diseases

Results from BeneGene-1 Study: Prospective collection of bleeding rate in hemophilia B patients prior to phase 3 study (BeneGene-2) of fidanacogene elaparvovec (ISTH 2023) - "316 hemophilia B patients were screened and 102 were enrolled and entered the study. nAb was positive in 193 participants and in part the cause of over 90% of screen failures. At the time of data cut, 59 had completed at least 6 months of follow-up, 40 had less than 6 months, and 3 patients had withdrawn."

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

FDA Accepts Pfizer’s Application for Hemophilia B Gene Therapy Fidanacogene Elaparvovec (Businesswire) - "Pfizer Inc...announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) for fidanacogene elaparvovec for the treatment of adults with hemophilia B. In parallel, the European marketing authorization application (MAA) for fidanacogene elaparvovec has also been accepted and is under review by the European Medicines Agency (EMA)....The submissions for fidanacogene elaparvovec are based on efficacy and safety data from the Phase 3 BENEGENE-2 study..."

BLA • European regulatory • Gene Therapies • Genetic Disorders • Hemophilia