Publications by authors named "G Avenard"
Article Synopsis
- Glenzocimab is a new antithrombotic drug that targets GPVI in platelets and aims to prevent bleeding, potentially addressing complications from SARS-CoV-2 which often causes blood clotting and lung damage.
- The GARDEN study tested glenzocimab against a placebo in hospitalized COVID-19 patients in Brazil and France, showing no significant difference in clinical progression of respiratory failure between the two groups, but a notable improvement in one specific health measure.
- Overall, glenzocimab did not increase bleeding risk, but its effectiveness for COVID-19-related acute respiratory distress syndrome wasn't confirmed, prompting further research, particularly in other medical conditions like stroke and cardiovascular issues.
Background: Antagonists of glycoprotein VI-triggered platelet activation used in combination with recanalisation therapies are a promising therapeutic approach in acute ischaemic stroke. Glenzocimab is an antibody fragment that inhibits the action of platelet glycoprotein VI. We aimed to determine and assess the safety and efficacy of the optimal dose of glenzocimab in patients with acute ischaemic stroke eligible to receive alteplase with or without mechanical thrombectomy.
View Article and Find Full Text PDFObjective- ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT017 in healthy subjects. Approach and Results- Six cohorts of 8 healthy male and female subjects each received ascending single doses of ACT017 (n=6) or placebo (n=2) as a 6-hour intravenous infusion, with ¼ of the total dose administered within 15 minutes and the rest of the dose (¾ of the total dose) administered within 5 hours and 45 minutes.
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- Monoclonal antibody fragments (Fab) are emerging as effective therapeutic agents, with various expression platforms like bacteria, yeast, and mammalian cells used for their production.
- The study compares the production of the humanized Fab fragment ACT017 from E. coli, Pichia pastoris, and CHO cells, noting that while E. coli yields high titer, it results in heterogeneous protein quality.
- Ultimately, CHO cells produce the most consistent protein quality, despite requiring longer culture times and higher production costs, offering important insights for future pharmaceutical development.
Glycoprotein VI is a platelet-specific collagen receptor critical for in vivo formation of arterial thrombosis. It is also considered as an attractive target for the development of anti-thrombotic drugs because blocking glycoprotein (GP)VI inhibits platelet aggregation without inducing detrimental effects on physiologic hemostasis. Here, we present data on the identification, in vitro and ex vivo pharmacology of a humanized Fab fragment designated as ACT017.
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