Prospective Efficacy and Safety of a Novel Bypassing Agent, FVIIa/FX Mixture (MC710) for Hemophilia Patients with Inhibitors

Tomokiyo, Kazuhiko; Nakatomi, Yasushi; Hamamoto, Takayoshi; Nakagaki, Tomohiro

doi:10.5772/27912

Cited by 3 publications

(4 citation statements)

References 52 publications

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“…It has been suggested that the surface of activated platelets might be the site where FVIIa activates FX in the haemostasis of bleeding of haemophilia patients by rFVIIa therapy . Enzymologic analysis has revealed that the K m for FVIIa‐catalyzed FX activation (0.16 to 0.25 μM) is higher than the FX concentration in plasma (approximately 8 μg mL −1 , 0.14 μM) in the presence or absence of TF, therefore, increased FX concentration in plasma would generate more FXa by FVIIa more quickly . Furthermore, the long half‐life of FX might contribute to its prolonged haemostatic potential in plasma.…”

Section: Discussionmentioning

confidence: 99%

A Phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics

et al. 2013

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MC710, a mixture of plasma-derived activated factor VII and factor X at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In a Phase II trial, we evaluated the haemostatic efficacy and safety of single doses of MC710, and investigated pharmacokinetic and pharmacodynamic parameters in nine joint bleeding episodes in six male haemophilia patients with inhibitors. This trial was a multi-centre, open-label, non-randomized study of two doses (60 and 120 μg kg(-1) as FVIIa dose), allowing the re-administration of different MC710 dosages to the same subjects. Haemostatic efficacy was assessed by evaluating reduction in pain and swelling, as well as increase in range of motion in a bleeding joint. The results of the study showed that in nine bleeding episodes, seven treatments were rated as 'excellent' or 'effective' according to investigator's rating system of efficacy at 8 h after administration. No serious or severe adverse events were observed after administration; furthermore, measurement of several diagnostic markers revealed no signs or symptoms of disseminated intravascular coagulation (DIC). The haemostatic potential of MC710 was confirmed at doses of 60 and 120 μg kg(-1) in this trial. MC710 is thus expected to be a safe and efficacious novel bypassing agent for controlling bleeding in haemophilia patients with inhibitors.

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Section: Discussionmentioning

confidence: 99%

A Phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics

et al. 2013

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show abstract

“…For the second dose, subjects were administered 60 or 120 μg kg −1 MC710 so that the total dose did not exceed 180 μg kg −1 . The dosage regime of MC710 was established based on the results from a preclinical study (thrombogenic test using monkeys) and phase I/II clinical studies . At least 20 bleeding episodes were planned to be treated during the study, and each subject was allowed to be treated for up to five episodes.…”

Section: Methodsmentioning

confidence: 99%

“…With the administration of 60–120 μg kg −1 MC710, FVIIa and FX levels in plasma should reach 1.5–2.0 μg mL −1 (30–40 n m ) and 20–35 μg mL −1 (400–700 n m ) respectively . Under these conditions, FX is increased 2.5–4.3 times the Km values (160 n m ) against FVIIa, and the enzyme reaction rate of FVIIa accelerates and approaches V max .…”

Section: Introductionmentioning

confidence: 99%

“…To minimize the risk of virus infection, there are three virus removal/inactivation steps in the MC710 production process: virus removal membrane filtration (average pore size of 15 nm), solvent/detergent treatment, and dry heating at 65°C for 96 h . MC710 promotes FVIIa‐mediated FX activation due to an enhanced enzyme/substrate (FVIIa/FX) reaction in the extrinsic pathway of blood coagulation, leading to increased thrombin generation and fibrin clot formation to stop bleeding . Further, FX has a longer half‐life than FVIIa, and blood FX levels will remain high after MC710 administration, even after FVIIa levels have decreased.…”

Section: Introductionmentioning

confidence: 99%

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