The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results

Kenet, Gili; Young, Guy; Chuansumrit, Ampaiwan; Matsushita, Tadashi; Yadav, Vandana; Zak, Marek; Male, Christoph

doi:10.1016/j.jtha.2023.07.030

Cited by 4 publications

(1 citation statement)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within treatment‐related factors, specific types of FVIII products have been studied across trial designs, including individual product PUP trials, the SIPPET trial, and the RODIN study 5,13 . Although some variability in rates has been reported, all available FVIII products that differ in cell of origin, presence of B domain, and/or various modifications generate clinically significant rates of inhibitors; direct comparison of inhibitor incidence between products is limited, as most studies were single armed and non‐randomized 5,13,24–26 . Albeit not inclusive of EHL R‐FVIII products or R‐FVIII products produced in human cell lines, the SIPPET trial provided insight on how fixed patient‐related and environmental factors may interact, as in a secondary analysis the ‘benefit’ of PD‐FVIII was most evident in participants with low‐risk genetic variants 27 …”

Section: Discussionmentioning

confidence: 99%

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Meeks,

Zimowski

2024

Haemophilia

View full text Add to dashboard Cite

IntroductionThe advent of therapeutic recombinant factor VIII (FVIII) and factor IX (FIX) protein infusions revolutionized the care of persons with haemophilia in the 1990s. It kicked off an era with the increasing use of prophylactic factor infusions for patients and transformed conversations around the ideal trough activity levels as well as the ultimate goals in tailored, individualized care. Our knowledge surrounding the immunologic basis of inhibitor development and treatment derives from a time when patients were receiving frequent factor infusions and focused on immune tolerance induction following inhibitor development.DiscussionMore recently, care was revolutionized again in haemophilia A with the approval of emicizumab, a bispecific antibody mimicking activated FVIII function, to prevent bleeding. The use of emicizumab prophylaxis has resulted in a significantly slower accumulation of factor exposure days and continued effective prophylaxis in the case of inhibitor development. While emicizumab is effective at reducing the frequency of bleeding events in patients with haemophilia A, management of breakthrough bleeds, trauma, and surgeries still requires additional treatment. Ensuring that FVIII is a therapeutic option, particularly for life‐threatening bleeding events and major surgeries is critical to optimizing the care of persons with haemophilia A. Other novel non‐factor concentrate therapies, including rebalancing agents, will dramatically change the landscape for persons with haemophilia B with inhibitors.ConclusionThis review discusses the changing landscape regarding the timing of inhibitor development and management strategies after inhibitor development, stressing the importance of education across the community to continue to vigilantly monitor for inhibitors and be prepared to treat persons with inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Meeks,

Zimowski

2024

Haemophilia

View full text Add to dashboard Cite

show abstract

International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia A and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology

Rezende,

Neumann,

Angchaisuksiri

et al. 2024

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Factor Replacement Treatment for Hemophilia A: Achievements and Perspectives

Mancuso

2024

Semin Thromb Hemost

View full text Add to dashboard Cite

The mainstay of treatment for persons with hemophilia A (PwHA) with severe bleeding phenotype is prophylaxis. The pharmacokinetic (PK) profile of native factor VIII (FVIII) imposes the need for rather frequent intravenous injections to ensure effective prophylaxis, but this represents a relevant treatment burden and is associated with suboptimal adherence to treatment. In this light, the advent of extended half-life (EHL) FVIII molecules has improved prophylaxis feasibility and outcomes by favoring treatment individualization and tailoring protection according to specific clinical and nonclinical needs. Different technologies have been used to enhance FVIII PK properties including Fc-fusion and conjugation with polyethylene glycol. Data from clinical development programs for such molecules, together with growing real-world experience, have shown numerous benefits related to the use of EHL FVIII in PwHA. Recently a new class of ultra-long-acting EHL FVIII has been developed to further improve protection against bleeding episodes and achieve the ambitious goal of providing PwHA with hemostatic protection in the nonhemophilia range over longer time periods, hence ensuring very low bleeding rates and improving joint health and quality of life. In this review, the achievements and perspectives of replacement therapies for PwHA are summarized and discussed.

show abstract

The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results

Cited by 4 publications

References 17 publications

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia A and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology

Factor Replacement Treatment for Hemophilia A: Achievements and Perspectives

Contact Info

Product

Resources

About