Glenzocimab: A GPVI (Glycoprotein VI)-Targeted Potential Antiplatelet Agent for the Treatment of Acute Ischemic Stroke
Issued Date
2022-11-01
Resource Type
ISSN
00392499
eISSN
15244628
Scopus ID
2-s2.0-85140658758
Pubmed ID
36128904
Journal Title
Stroke
Volume
53
Issue
11
Start Page
3506
End Page
3513
Rights Holder(s)
SCOPUS
Bibliographic Citation
Stroke Vol.53 No.11 (2022) , 3506-3513
Suggested Citation
Wichaiyo S., Parichatikanond W., Rattanavipanon W. Glenzocimab: A GPVI (Glycoprotein VI)-Targeted Potential Antiplatelet Agent for the Treatment of Acute Ischemic Stroke. Stroke Vol.53 No.11 (2022) , 3506-3513. 3513. doi:10.1161/STROKEAHA.122.039790 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85412
Title
Glenzocimab: A GPVI (Glycoprotein VI)-Targeted Potential Antiplatelet Agent for the Treatment of Acute Ischemic Stroke
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
It has previously been shown in several animal experiments that platelet GPVI (glycoprotein VI) contributes to thrombosis, particularly in ischemic stroke. Moreover, GPVI levels are upregulated in stroke patients. This review describes the therapeutic roles of anti-GPVI antibody in preclinical models of ischemic stroke and provides the current evidence for potential benefits of glenzocimab, a Fab fragment of humanized anti-GPVI monoclonal antibody, in stroke patients. Anti-GPVI antibody, JAQ1, significantly decreased infarct volume and improved neurological function in mice with transient middle cerebral artery occlusion, a model of ischemic stroke, with no or minor bleeding tendency. Intravenous injection of glenzocimab in nonhuman primates produced rapid inhibition of ex vivo platelet aggregation induced by collagen (a GPVI ligand). Complete platelet inhibition is observed at 30 minutes following administration without increasing the risk of bleeding. In humans, glenzocimab is well tolerated and produces dose-dependent antiplatelet activity. More importantly, glenzocimab (125-1000 mg) was safe when administered as soon as possible (<3 hours) following reperfusion with the r-tPA (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke. Although glenzocimab 1000 mg (a selected dose) did not demonstrate a significant improvement in overall clinical outcomes, it appeared to provide benefits in severe cases and in patients who required thrombectomy. This promising efficacy together with a good safety profile of glenzocimab warrant further investigation in phase III (ACTISAVE [Adaptive Efficacy and Safety Study of Glenzocimab Used as an Add-On Therapy on Top of Standard of Care in the 4.5 Hours Following an Acute Ischemic Stroke]) clinical study.