Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial.

Background: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

Objectives: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

Methods: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10 vg/kg infusion of valoctocogene roxaparvovec.

Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography.

Background: Recurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia, despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient's assessment of musculoskeletal pain may not accurately identify a joint bleed.

International Society on Thrombosis and Haemostasis Clinical Practice Guideline for Treatment of Congenital Haemophilia-A Critical Appraisal.

Introduction: Evidence-based clinical practice guidelines drive optimal patient care and facilitate access to high-quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non-randomized and well-designed observational studies and real-world data, is challenging. The methodology used for assessing available evidence should consider this critical fact.

Cost of hemophilia A in Brazil: a microcosting study.

Background: Patients with Hemophilia are continually monitored at treatment centers to avoid and control bleeding episodes. This study estimated the direct and indirect costs per patient with hemophilia A in Brazil and evaluated the cost variability across different age groups.

Methods: A prospective observational research was conducted with retrospective data collection of patients assisted at three referral blood centers in Brazil.

The translational gap for gene therapies in low- and middle-income countries.

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical scope of gene therapies expands, consideration must be given to those who will benefit and what proactive steps must be taken to widen development and access potential, particularly in regions carrying a high disease burden.

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A.

Introduction: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control.

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.

Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial.

Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis.

Promoting pain coping skills in haemophilia: A remote intervention integrating exercise and pain education.

Background: Chronic joint pain is a significant and widespread symptom in people with haemophilia (PWH). Despite medical advancements, effective pain management remains challenging.

Aim: This study presents an innovative approach that integrates remote physical exercises, pain neuroscience education, and coping strategies to address chronic pain in PWH.

The effectiveness and safety of octocog alfa in patients with hemophilia A: up to 7-year follow-up of the real-world AHEAD international study.

Background: Real-world data assessing treatment outcomes in patients with hemophilia A in routine clinical practice are limited.

Objective: To evaluate the effectiveness and safety of octocog alfa in patients with moderate/severe hemophilia A receiving treatment in clinical practice.

Design: The international Antihemophilic Factor Hemophilia A Outcome Database study is an observational, noninterventional, prospective, multicenter study.

EFFECTIVENESS OF VISCOSUPPLEMENTATION IN THE TREATMENT OF HEMOPHILIC ARTHROPATHY: A SYSTEMATIC REVIEW.

Objective: To describe the efficacy of using viscosupplementation in patients with hemophilic arthropathy (HA), on pain, limb functionality, and quality of life.

Methods: A systematic review of the literature was performed following the PRISMA guidelines without limitations of language or year of publication. The search was performed on the following medical databases: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost, and PROQUEST in April 2020.

Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1.

Background: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL).

Objectives: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1.

Methods: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS).

A review of the rationale for gene therapy for hemophilia A with inhibitors: one-shot tolerance and treatment?

The therapeutic landscape for people living with hemophilia A (PwHA) has changed dramatically in recent years, but many clinical challenges remain, including the development of inhibitory antibodies directed against factor VIII (FVIII) that occur in approximately 30% of people with severe hemophilia A. Emicizumab, an FVIII mimetic bispecific monoclonal antibody, provides safe and effective bleeding prophylaxis for many PwHA, but clinicians still explore therapeutic strategies that result in immunologic tolerance to FVIII to enable effective treatment with FVIII for problematic bleeding events. This immune tolerance induction (ITI) to FVIII is typically accomplished through repeated long-term exposure to FVIII using a variety of protocols.

Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR.

Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B.

Long-term efficacy and safety of the extended half-life recombinant factor IX Fc fusion protein (rFIXFc) has been established among previously treated patients with severe hemophilia B in 2 phase 3 trials (B-LONG [#NCT01027364] and Kids B-LONG [#NCT01440946]) and a long-term extension study (B-YOND [#NCT01425723]). In this study, we report post hoc analyses of pooled longitudinal data for up to 6.5 years for rFIXFc prophylaxis.

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.

Gene therapy for hemophilia: looking beyond factor expression.

Hemophilia A (factor VIII [FVIII] deficiency) and hemophilia B (factor IX [FIX] deficiency) are the X-linked recessive bleeding disorders that clinically manifest with recurrent bleeding, predominantly into muscles and joints. In its severe presentation, when factor activity is less than 1% of normal, hemophilia presents with spontaneous musculoskeletal bleeds and may progress to debilitating chronic arthropathy. Management of hemophilia has changed profoundly in the past decades.

Extended half-life recombinant factor VIII treatment of hemophilia A in Brazil: an expert consensus statement.

Introduction: Treatment of hemophilia A in Brazil is offered to all patients at no cost. However, several unmet medical needs exist.

Method: In this study, we applied the Delphi method to discuss with seven hemophilia A specialists the challenges that patients and the health system face regarding hemophilia A treatment and opportunities for improvement.