Anti-GPVI Fab SAR264565 effectively blocks GPVI function in ex vivo human platelets under arterial shear in a perfusion chamber

European Journal of Clinical Pharmacology
Peter FlorianJochen Graff

Abstract

Glycoprotein VI (GPVI) is the major platelet receptor for collagen-mediated platelet adhesion and activation. SAR264565 is an anti-GPVI-Fab, binds to GPVI with high affinity, and blocks GPVI function in human platelets in vitro. The effect of SAR26456 on platelet responsiveness in the blood of 21 healthy male subjects was investigated using Sakariassen's ex vivo thrombogenesis perfusion chamber model on a collagen-coated surface under conditions mimicking arterial flow. Ex vivo effects of SAR264565 (10 and 100 μg/mL) were investigated before administration of aspirin or clopidogrel to study subjects (baseline), after aspirin (2× 300 mg) administration alone, and after combined aspirin (2× 300 mg)/clopidogrel (600 mg) administration. Additional ex vivo and in vitro platelet tests were also performed. Addition of SAR264565 to the perfusion chamber dose-dependently reduced platelet and fibrin deposition, reaching statistical significance at 100 μg/mL (415 ± 67 compared to 137 ± 36 platelets/cm2, [p < 0.01] and fibrin 0.095 ± 0.014 compared to 0.032 ± 0.008 μg/cm2, [p < 0.001]). Aspirin administration caused an additive and dose-dependent reduction of SAR264565-induced platelet and fibrin deposition. Combined aspirin/clopidogrel ad...Continue Reading

References

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Citations

Jun 13, 2020·Platelets·Fawaz O Alenazy, Mark R Thomas
Aug 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dina VaraGiordano Pula
Dec 15, 2020·Platelets·Maan H HarbiMark R Thomas
Apr 4, 2021·Cancers·Philipp von Hundelshausen, Wolfgang Siess
May 29, 2020·Journal of Medicinal Chemistry·Holly FosterRichard Foster

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Methods Mentioned

BETA
ELISA
flow cytometry

Clinical Trials Mentioned

NCT01645306

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