Rurioctocog alfa pegol 2,000unit powder and solvent for solution for injection vials

IntroductionInhibitor development is a primary concern for pediatric patients with hemophilia A (HA) undergoing recombinant factor VIII (rFVIII) therapy, yet relevant research is lacking. We aimed to compare the efficacy and safety of standard (SHL) and extended half-life (EHL) rFVIII products in previously treated (PTPs) and untreated (PUPs) pediatric patients with HA.MethodsFollowing PRISMA guidelines, we searched clinical studies from PubMed, Embase, and Cochrane Library. Data were extracted and a single-arm meta-analysis was performed.ResultsThis systematic review included 16 studies involving 1145 patients. Three studies reported changes in annual bleeding rate (ABR); their results displayed no statistically significant difference in ABR changes in pediatric patients with HA after rFVIII treatment. Ten studies reported inhibitor development, nine focused on PUPs. Here, EHL rFVIII showed a proportion of inhibitors at 27.5% (95% confidence interval [CI] 22.6%; 32.6%), and third-generation SHL rFVIII showed a proportion of inhibitors at 36.4% (27.2%; 46.2%), with a high-titer proportion of 20.9% (12.9%; 30.3%) for the latter. Both SHL rFVIII (octocog alfa) and EHL rFVIII (rurioctocog alfa pegol) presented low proportions of inhibitor development. Octocog alfa exhibited the lowest high-titer inhibitor incidence, marked at 12.7% (5.3%; 24.5%). Eleven studies addressed adverse events (AEs), with octocog alfa showing low reported treatment-related AEs at a proportion of 14.5% (6.5%; 26.7%).ConclusionOur analysis revealed that both octocog alfa and rurioctocog alfa pegol showed low inhibitor development, with octocog alfa having few treatment-related AEs. Regular monitoring for inhibitors during rFVIII therapy is important.

Abstract licence: CC BY-NC

Background: Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. Methods: This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Results: Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04-3.14) and 92% (95% CI = 85%-97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Conclusions: Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.

Abstract licence: CC BY 4.0

Background: Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. Methods : This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Results: Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04–3.14) and 92% (95% CI = 85%–97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Conclusions: Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.

Abstract licence: CC BY 4.0

Factor VIII (FVIII) is an important component of blood coagulation as its congenital deficiency results in life-threatening bleeding. Current prophylactic therapy of the disease (hemophilia A) is based on 3-4 intravenous infusions of therapeutic FVIII per week. This poses a burden on patients, demanding reduction of infusion frequency by using FVIII with extended plasma half-life (EHL). Development of these products requires understanding FVIII plasma clearance mechanisms. This paper overviews (i) an up-to-date state of the research in this field and (ii) current EHL FVIII products, including recently approved efanesoctocog alfa, for which the plasma half-life exceeds a biochemical barrier posed by von Willebrand factor, complexed with FVIII in plasma, which results in ~1 per week infusion frequency. We focus on the EHL FVIII products' structure and function, in particular related to the known discrepancy in results of one-stage clotting (OC) and chromogenic substrate (CS) assays used to assign the products' potency, dosing, and for clinical monitoring in plasma. We suggest a possible root cause of these assays' discrepancy that is also pertinent to EHL factor IX variants used to treat hemophilia B. Finally, we discuss approaches in designing future EHL FVIII variants, including those to be used for hemophilia A gene therapy.

Abstract licence: CC BY

Background and Clinical Significance: Hemophilia A presents a considerable challenge in cardiac surgery due to the elevated risk of perioperative bleeding, particularly during procedures involving cardiopulmonary bypass. Standard management typically involves standard half-life (SHL) factor VIII (FVIII) concentrates, which require frequent dosing. Extended half-life (EHL) FVIII products offer theoretical advantages, including prolonged action and reduced infusion frequency, but their use in cardiac surgery remains largely undocumented. Case Presentation: We report the case of a 73-year-old male with mild Hemophilia A who underwent successful aortic valve replacement using a 25 mm Carpentier-Edwards Magna Ease biological prosthesis. The patient was managed perioperatively with an anti-hemorrhagic protocol based on EHL recombinant FVIII. The surgery and postoperative course were uneventful, with no bleeding complications or need for transfusion. Conclusions: This case illustrates the potential role of EHL FVIII in safely managing hemophilic patients undergoing major cardiac surgery. Given the lack of existing reports in the literature, further studies are warranted to evaluate the efficacy and safety of EHL FVIII in this setting and to potentially optimize perioperative care protocols for this patient population.

Abstract licence: CC BY 4.0