Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies.

Long-Term Efficacy and Safety of Damoctocog Alfa Pegol Prophylaxis in Patients with Haemophilia A Aged 12-<18 Years at Enrolment into PROTECT VIII.

Introduction: The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12-<18 years at enrolment.

Method: PROTECT VIII was a multicentre, open-label study of previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%).

Interim analyses of the multinational real-world prospective cohort HEM-POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A.

Objectives: To assess effectiveness and safety of damoctocog alfa pegol in interim analyses of the ongoing real-world hemophilia A HEM-POWR study.

Methods: HEM-POWR (NCT03932201) is a multinational Phase 4 prospective observational study. The primary objective was annualized bleeding rate (ABR) in previously treated patients (PTPs) with hemophilia A.

Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: analysis from the PROTECT VIII study.

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities.

Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities to transform the care of people with hemophilia.

Background: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A.

Background: Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously.

Methods: We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×10 vector genomes of valoctocogene roxaparvovec per kilogram of body weight.

A laparoscopic approach to address massive splenomegaly, symptomatic cholelithiasis, and a planned postoperative pregnancy: A case report.

We report long-term follow-up of a patient who underwent a tailored laparoscopic procedure for symptomatic cholelithiasis, massive splenomegaly, and a planned pregnancy. There were no complications, and the patient remained symptom-free at the 5-year follow-up. We supplemented our case report with national surgical data demonstrating the safety of laparoscopic splenectomy.

Prophylaxis use of clotting factor replacement products in people with non-severe haemophilia: A review of the literature.

Introduction: People with non-severe haemophilia appear to be under-treated in many countries, and this may lead to joint damage and worsen quality of life.

Aim: To review literature for clotting factor replacement prophylaxis in people with non-severe haemophilia A and B (HA/HB) in relation to long-term outcomes to support clinical decision-making.

Methods: A targeted literature search was performed to identify studies published between 2000 and 2021 that included prophylaxis in people with non-severe HA/HB and long-term outcomes, including annualized bleeding rates, joint health and quality of life.

Clinical studies of extended-half-life recombinant FVIII products for prophylaxis in adults and children: A critical review from the physician's perspective.

This review compares the methodology of published clinical studies investigating the extended-half-life (EHL) factor VIII (FVIII) products, rFVIIIFc (efmoroctocog alfa, Elocta®/Eloctate®), BAY 94-9027 (damoctocog alfa pegol, Jivi®), BAX 855 (rurioctocog alfa pegol, Adynovate®) and N8-GP (turoctocog alfa pegol, Esperoct®) including the phase 2/3 studies, A-LONG (NCT01181128), PROTECT VIII (NCT01580293), PROLONG-ATE (NCT01736475) and pathfinder2 (NCT01480180), respectively, and their corresponding pediatric studies and extensions. Study results are interpreted from a treating physician's perspective, translating into evidence-based, real-life use of the different EHL recombinant FVIII products for personalized prophylaxis. The similarities between the studies include methodology, objectives, study design and cohort size.

Integrated Hemophilia Patient Care via a National Network of Care Centers in the United States: A Model for Rare Coagulation Disorders.

Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, and emotional needs of people with hemophilia (PWH) and may serve as a model for other rare coagulation disorders. Health-care purchasers, as well as the general medical community, may not appreciate the breadth and quality of services provided by HTCs.

PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors.

Introduction: Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.

Aim: To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3.

Confirmed long-term safety and efficacy of prophylactic treatment with BAY 94-9027 in severe haemophilia A: final results of the PROTECT VIII extension study.

Introduction: The phase 2/3 PROTECT VIII main study demonstrated efficacy and safety of BAY 94-9027 (damoctocog alfa pegol; Jivi ), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to extend its half-life.

Aim: To report the final efficacy and safety data for BAY 94-9027 from the PROTECT VIII extension.

Methods: Previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%) who completed the multicentre, open-label PROTECT VIII main study were eligible for the extension.

Decreased Bleeding Rates in Patients with Hemophilia A Switching from Standard-Half-Life FVIII to BAY 94-9027 Prophylaxis.

BAY 94-9027 (damoctocog alfa pegol, Jivi) is an extended-half-life recombinant factor VIII (rFVIII) shown to be well-tolerated and efficacious in bleeding prevention in previously treated patients with severe hemophilia A. During the PROTECT VIII study, prophylaxis patients received BAY 94-9027 at intervals determined based on their bleeding phenotype, observed during a 10-week run-in treatment period with twice-weekly dosing. Those with ≤ 1 spontaneous joint or muscle bleed were randomized to either 45 to 60 IU/kg every 5 days or 60 IU/kg every 7 days; patients could increase dosing frequency to every 5 days or twice weekly in the case of bleeds.

Opioid exposure in haemophilia patients is common and underreported.

Introduction: In an era of increased opioid awareness, data on opioid exposure in haemophilia patients are lacking.

Aim: The objectives of this study were to (a) provide a detailed description of opioid exposure in haemophilia patients based on written prescription data, (b) compare our findings to national haemophilia-specific and general population datasets and (c) identify predictors of opioid exposure in haemophilia patients.

Methods: Medical records of 183 adult and 135 paediatric patients from two haemophilia treatment centres (HTC) were reviewed over a 42-month period.

BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results.

Introduction: BAY 94-9027 is an extended-half-life, site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks.

Aim: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years.

Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during surgery in patients with severe hemophilia A: Results of the PROTECT VIII clinical trial.

Introduction: Ensuring hemostasis during invasive procedures is a challenge in patients with severe hemophilia A. This analysis evaluated efficacy and safety of BAY 94-9027, an extended-half-life recombinant factor VIII (FVIII), in the surgical setting.

Materials And Methods: Patients participating in an open-label BAY 94-9027 clinical trial who underwent major surgery were included in the analysis.

Reversal of acquired von Willebrand syndrome with allogeneic stem cell transplant for chronic lymphocytic leukemia.

Acquired von Willebrand syndrome (AVWS) is a rare, potentially fatal bleeding disorder caused by low activity of von Willebrand factor (VWF) in patients without congenital deficiency. The majority of adult cases are associated with hematological malignancy, including lymphoproliferative (48%) or myeloproliferative (15%) disorders (Federici et al., 2000).

Catheter-Related Thrombosis in Patients with Lymphoma or Myeloma Undergoing Autologous Stem Cell Transplantation.

Catheter-related thrombosis (CRT) occurs frequently during autologous hematopoietic cell transplantation (AHCT) and data regarding the incidence, risk factors, and management are understudied. We evaluated 789 consecutive patients with lymphoma and myeloma that underwent AHCT over 10 years (2006 to 2016) and detected the incidence of CRT was 6.3%; only 32% of CRT were symptomatic.

Anti-factor Xa and activated partial thromboplastin time measurements for heparin monitoring in mechanical circulatory support.

Objectives: This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs).

Background: CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology.