Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A.

@article{Shima2016FactorVF,
  title={Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A.},
  author={Midori Shima and Hideji Hanabusa and Masashi Taki and Tadashi Matsushita and Tetsuji Sato and Katsuyuki Fukutake and Naoki Fukazawa and Koichiro Yoneyama and Hiroki Yoshida and Keiji Nogami},
  journal={The New England journal of medicine},
  year={2016},
  volume={374 21},
  pages={
          2044-53
        }
}
BACKGROUND In patients with severe hemophilia A, standard treatment is regular prophylactic and episodic intravenous infusions of factor VIII. However, these treatments are burdensome, especially for children, and may lead to the formation of anti-factor VIII alloantibodies (factor VIII inhibitors). Emicizumab (ACE910), a humanized bispecific antibody mimicking the cofactor function of factor VIII, was developed to abate these problems. METHODS We enrolled 18 Japanese patients with severe… 
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Emicizumab for the treatment of acquired hemophilia A.
TLDR
Emicizumab seems to be an effective hemostatic therapy for AHA, with the advantages of sc.
Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors
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Empicizumab prophylaxis administered subcutaneously once weekly or every 2 weeks led to a significantly lower bleeding rate than no proPHylaxis among persons with hemophilia A without inhibitors; more than half of the participants who received prophYLaxis had no treated bleeding events.
Evaluating the safety of emicizumab in patients with hemophilia A
TLDR
Thrombotic complications including TMA, not seen with other bypassing agents, raises concern about the use of emicizumab in combination with aPCC and how patients who have breakthrough bleeding can be safely managed.
Emicizumab Prophylaxis in Hemophilia A with Inhibitors
TLDR
Empicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no proPHylaxis among participants with hemophilia A with inhibitors and resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing‐agent prophylum.
Bridging the Missing Link with Emicizumab: A Bispecific Antibody for Treatment of Hemophilia A
TLDR
Empicizumab is the first humanized bispecific monoclonal therapeutic antibody designed to replace the hemostatic function of activated FVIII by bridging activated factor IX and factor X (FX) to activate FX and allow the coagulation cascade to continue.
Bispecific Antibodies and Advances in Non–Gene Therapy Options in Hemophilia
  • M. Shima
  • Biology, Medicine
    Research and practice in thrombosis and haemostasis
  • 2020
TLDR
In general, emicizumab proved to be well tolerated, although isolated thromboembolic and thrombotic microangiopathic complications were observed in the HAVEN 1 studies, and 3 out of a total of 400 patients developed neutralizing antidrug antibodies.
Spotlight on emicizumab in the management of hemophilia A: patient selection and special considerations
TLDR
There is no doubt that emicizumab is an alternate first-line therapy for any existing BPA as hemostatic treatment for PwHA with inhibitor, but one should be more cautious in combination with aPCC on breakthrough bleeds under emicIZumab prophylaxis because of thrombotic risk.
Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A.
TLDR
Current laboratory monitoring methods, including activated partial thromboplastin time, FVIII one-stage clotting assays, F VIII chromogenicAssays, and global coagulations assays are discussed and suggested, to suggest alternative methods applicable to monitoring HA treatment in an evolving treatment landscape.
New therapies using nonfactor products for patients with hemophilia and inhibitors.
TLDR
The current findings have demonstrated that prophylaxis by nonfactor products supports marked reductions of bleeding episodes in hemophilia patients with or without inhibitor.
Exposure–Bleeding Count Modeling of Emicizumab for the Prophylaxis of Bleeding in Persons with Hemophilia A with/Without Inhibitors Against Factor VIII
TLDR
Exposure–response relationship between emicizumab concentrations and bleeding frequency is described and adequate bleeding control of the investigated dosing regimens 1.5 mg/kg once weekly, 3mg/kg every 2 weeks, and 6 mg/ kg every 4 weeks is confirmed.
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