Moroctocog alfa 500unit powder and solvent for solution for injection pre-filled syringes

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

Bu çalışmada çok boyutlu ölçümlerde iç tutarlık anlamında güvenirliğin değerlendirilmesinde Cronbach alfa katsayısı yerine daha uygun alternatiflerini kullanma konusunda farkındalık oluşmasına katkı sağlamak amaçlanmıştır. Bu amaç kapsamında örneklem büyüklüğü (100, 200 ve 400), boyutlar arası korelasyon (0,00 ve 0,50), maddeler arası korelasyon (0,30-0,50 ve ≥0,75), test uzunluğu (10 ve 20) ve boyutlara düşen madde sayısı (5-5, 7-3, 10-10 ve 15-5) koşulları altında iki boyutlu basit ve karmaşık test yapılarında üretilen verilerde alfa, tabakalı alfa ve omega katsayılarının performansı incelenmiştir. Ayrıca araştırmacılara tabakalı alfa ve omega katsayılarının manuel olarak kolaylıkla hesaplanabildiğini göstermek amacıyla örnekler sunulmuştur. Veriler R programı ile psych ve sirt paketleri kullanılarak analiz edilmiştir. Araştırmanın sonucunda güvenirlik kestirimleri üzerinde en fazla etkisi olan değişkenlerin sırasıyla maddeler arası korelasyon ve boyutlar arası korelasyon olduğu bulunmuştur. Test uzunluğunun ilişkisiz modellerde maddeler arası düşük korelasyon koşulu altında güvenirlik kestirimleri üzerinde daha fazla etkiye sahip olduğu görülmüştür. Örneklem büyüklüğü ortalama güvenirlik kestirimleri üzerinde etkili bulunmamıştır ancak kestirimlerin hatası üzerinde etkili bulunmuştur. Omega ve tabakalı alfa katsayılarının performansı benzer bulunurken alfa katsayısı ise bu katsayılardan daha düşük güvenirlik değerleri kestirmiştir. Hem alanyazına hem de mevcut çalışmanın sonuçlarına dayalı olarak araştırmacılara, çok boyutlu ölçümlerde iç tutarlılık anlamında güvenirlik kanıtı olarak alfa katsayısını kullanmamaları ya da tek başına kullanmamaları; bunun yerine omega, tabakalı alfa gibi daha uygun katsayıları kullanıp raporlamaları önerilir.

Abstract licence: CC BY-NC

Patients with hemophilia A and B who have inhibitors face limited treatment options, because replacement therapy with clotting factor VIII or IX concentrates is ineffective, particularly for patients with high-titer inhibitors. Current mainstay therapies include immune tolerance induction (through frequent injections of clotting factor VIII or IX concentrates) to eradicate inhibitors and bypassing agents (such as recombinant activated clotting factor VII and activated prothrombin complex concentrates) for the prevention and treatment of bleeding episodes. The use of these agents typically requires intravenous injections and sometimes hospitalization, which can be burdensome for patients. More recently, emicizumab, a bispecific antibody that mimics the function of activated clotting factor VIII, has demonstrated favorable efficacy for prophylaxis in patients with hemophilia A and inhibitors, representing a promising new therapeutic strategy. Ongoing research aims to discover and develop easy-to-use nonfactor agents for managing hemophilia with inhibitors. This review summarizes the current understanding of the pathophysiology of inhibitor development in hemophilia, outlines existing treatment options, and discusses advancements in novel therapeutic biologics, including a recombinant activated clotting factor VII variant (marzeptacog alfa), a new bispecific antibody (Mim8), antitissue factor pathway inhibitor antibodies (concizumab and marstacimab), and small interfering RNA targeting antithrombin (fitusiran). All of these agents are administered subcutaneously, with some offering the convenience of less frequent dosing (e.g., weekly or monthly). These potential drug candidates may provide significant benefits for the prophylaxis or treatment of bleeding disorders in patients with hemophilia and inhibitors.

Abstract licence: CC BY

BackgroundIn the earlier PROTECT VIII Kids study (NCT01775618), damoctocog alfa pegol was efficacious for prevention and treatment of bleeds in children aged ObjectiveAssess the safety of damoctocog alfa pegol, including hypersensitivity and loss of efficacy (LoE) due to an immune response to polyethylene glycol, in children aged 7 to MethodsAlfa-PROTECT is a phase 3, multicentre, open-label, single-arm study (NCT05147662). Primary endpoint was the incidence of adverse events of special interest (AESI) leading to discontinuation during the first 4 exposure days.ResultsOverall, 35 children enrolled; 32 completed the 6-month study, 21 (60%) reported ≥ 1 AE. Median (range) treatment duration was 182 (172-198) days. All AEs were mild/moderate; 3/35 children (8.6%) had study drug-related AEs. One (2.9%) LoE event was considered an AESI, and led to temporary treatment interruption. No AEs resulted in study drug discontinuation. The probability of ConclusionsThese data confirm the safety profile of damoctocog alfa pegol in children aged 7 to Trial registrationThe Alfa-PROTECT trial is registered at ClinicalTrial.gov (NCT05147662).

Abstract licence: CC BY-NC