Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A

Wang, Cassandra P; Young, Guy; Thornburg, Courtney D.

doi:10.1080/14740338.2021.1893303

Cited by 5 publications

(8 citation statements)

References 54 publications

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“…This approach may be more relevant in patients with inhibitors where breakthrough bleeds require combined therapy with emicizumab and bypassing agents, which may represent a certain risk of thrombotic complications. 17 The risk of thrombosis associated with TxAc and other procoagulant molecules including bypassing agents is not very high and such associations are widely used in clinics. [18][19][20][21] Moreover TxAc is a widely available low cost molecule.…”

Section: Resultsmentioning

confidence: 99%

“…According to the preclinical data presented above, we may speculate that in patients with history of breakthrough bleeds while on prophylaxis with emicizumab, whether that is a result of a partial individual response to emicizumab or increased haemostasis requirements based on the lifestyle of the patient, TxAc may be a good adjunctive therapy in certain patients, especially when used before physical activity. This approach may be more relevant in patients with inhibitors where breakthrough bleeds require combined therapy with emicizumab and bypassing agents, which may represent a certain risk of thrombotic complications 17 . The risk of thrombosis associated with TxAc and other procoagulant molecules including bypassing agents is not very high and such associations are widely used in clinics 18–21 .…”

Section: Resultsmentioning

confidence: 99%

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Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study

et al. 2021

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Background: Patients with severe haemophilia have impaired haemostatic response, delayed clot formation and fibrin clots that are vulnerable to fibrinolysis. Emicizumab is a bispecific antibody that mimics activity of activated factor VIII (FVIII) and increases haemostatic capacity to the level of moderate-to-mild haemophilia, thereby used for prophylaxis. Regardless of the impressive clinical performance of emicizumab, breakthrough bleeds may still occur. We aimed to study, in FVIII knockout mice (FVIII-KO), whether haemostasis is improved with the addition of tranexamic acid (TxAc) to emicizumab.Methods: FVIII-KO mice received prophylaxis with emicizumab or emicizumab+TxAc before trauma. FVIII-KO mice were given emicizumab 1.5 mg/kg via IV injection. A second retro-orbital IV injection containing human FIX and FX (both 100U/kg) was given 24 h later and 5 min before the tail amputation or knee trauma. After trauma-induced knee joint bleeding, magnetic resonance imaging (MRI), and histological analysis were used to compare haemostatic efficacy of the two prophylactic strategies. Thrombin generation (TG) was measured and clots obtained with TG experiment were analysed by scanning electron microscopy. Results:In FVIII-KO mice, blood loss after tail clip was lower after prophylaxis with emicizumab+TxAc compared to emicizumab. MRI results and histological analysis of knee joints showed that the addition of TxAc significantly decreased joint bleeding. Fibrin fibre diameters of mice treated with emicizumab only was thicker than those who received combined prophylaxis with emicizumab+TxAc. Conclusion:Our results suggest a potential benefit of TxAc when used in combination with emicizumab in prophylactic settings, especially in patients presenting breakthrough bleeds.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study

et al. 2021

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“…Emicizumab is a bi-specific factor VIIIa mimetic that substitutes the function of FVIII. 4 It has a long half-life and SQ administration and is widely prescribed for haemophilia A prophylaxis with demonstrated superiority to factor prophylaxis. 5 There is not a similar substitution therapy for haemophilia B.…”

Section: Backg Rou N Dmentioning

confidence: 99%

The benefits of gene therapy in people with haemophilia

Thornburg

2024

Journal of Viral Hepatitis

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Haemophilia is an inherited bleeding disorder which causes significant morbidity and mortality, especially in the severe form. Prophylaxis with factor replacement has high efficacy in reducing bleeding but is limited by the need for frequent intravenous infusion and fluctuations in haemostasis between doses. Additional prophylaxis therapies are being developed which may overcome some of the current treatment barriers. Gene therapy (GT) is being developed to provide a functional cure such that there is sustained factor expression and minimal to no need for additional haemostatic therapy. There are now two approved gene therapies for haemophilia which may be transformative for many individuals. Benefits of GT should go beyond increasing factor activity and reducing bleeding as persons with haemophilia aim to achieve a ‘haemophilia‐free mind’ and health equity with optimal health and well‐being.

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“…A solution to replace the prophylactic substitution of FVIII is emicizumab (ACE910) -a bispecific-humanized monoclonal antibody able to improve coagulation by bridging activated factor IX and factor X (ref. 21 ). It activates factor X and allows the coagulation cascade to continue 22 .…”

Section: Treatment With Emicizumabmentioning

confidence: 99%

“…Emicizumab managed to reduce the number of hemorrhagic events compared to both on-demand and prophylactic substitution therapy. It has an excellent safety profile; only rare cases of thrombotic microangiopathy and thrombotic event are reported 21 . It is subcutaneously delivered and much less often compared to factor VIII products.…”

Section: Treatment With Emicizumabmentioning

confidence: 99%

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A

Mihăilă¹

2023

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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The treatment of hemophilia A has progressed amazingly in recent years. Emicizumab, a bispecific-humanized monoclonal antibody, is able to improve coagulation by bridging activated factor IX and factor X. Emicizumab is administered subcutaneously and much less often compared to factor VIII products. It has low immunogenicity, does not require dose adjustment, and can be administered regardless of the presence of factor VIII inhibitors. Thrombin generation assays but not factor VIII activity are indicated to guide and monitor the treatment. Emicizumab has enabled the conversion of patients with severe forms into patients with milder forms of hemophilia A. It has reduced the number of bleeding episodes compared to both on-demand and prophylactic substitution therapy and has an excellent safety profile. Gene therapy can elevate factor VIII plasma levels for many years after a single treatment course, could offer longterm protection from bleeding episodes, and minimize or eliminate the need for substitutive treatment with factor VIII concentrates. Gene therapy can provoke an immune response, manifested by an increase in common liver enzymes, that require immunotherapy. Long term monitoring is necessary to identify possible adverse effects. Future objectives are: the development of an ideal viral vector, the possibility of its re-administration, the use of gene therapy in hemophiliac children, and determining whether it can be successfully used to induce immune tolerance to factor VIII ceteri paribus. The future will determine the place of each type of treatment and group of patients for which it is indicated.

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Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A

Cited by 5 publications

References 54 publications

Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study

Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study

The benefits of gene therapy in people with haemophilia

From a bispecific monoclonal antibody to gene therapy: A new era in the treatment of hemophilia A

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