Key result
APT402 cuts arterial thrombus weight ~95% vs. placebo in rabbits without increasing bleeding time.
Why the study?
Antithrombotic therapy is essential for thrombotic conditions, but current antithrombotic drugs cause bleeding that limits dose and clinical effectiveness.
Does APT402 prevent thrombosis without increasing bleeding in preclinical models of arterial and venous thrombosis?
Does APT402 prevent thrombosis without increasing bleeding in preclinical models of arterial and venous thrombosis?
Effect estimate: 95% reduction
Absolute Event Rate: 0.4% vs 7.8%
APT402, a novel apyrase-annexin V fusion protein, effectively prevents arterial and venous thrombosis in animal models without increasing bleeding risk.
Supports further preclinical development of APT402; leaves open translation to human thrombosis prevention without bleeding.
Antithrombotic therapy is essential to prevent thrombotic reocclusion in patients with acute myocardial infarction, stroke, or venous thromboembolism. However, current antithrombotic drugs cause bleeding that limits dose and clinical effectiveness. Previously, we reported that APT102 (AZD3366), a human apyrase optimized to scavenge extracellular ADP and ATP, exhibited potent antiplatelet efficacy without bleeding in experimental myocardial infarction and stroke. Here we describe APT402, an optimized fusion of APT102 and annexin V that uniquely inhibits both platelet and coagulation components of thrombus growth. APT402 preferentially bound to injured vessels and thrombus and prevented thrombotic occlusion in arterial and venous thrombosis models, without increasing bleeding. Thus, APT402 breaks the confounding link between antithrombotic efficacy and bleeding, pioneering a safe and effective approach to prevent and treat a broad range of thrombotic diseases, and may be particularly useful in clinical conditions associated with high bleeding risks.
No takes yet. Share an insight, caveat, or question.
Chen et al. (2021) studied Arterial and venous thrombosis. APT402 vs. Placebo was evaluated on Arterial thrombus weight (mg) (95% reduction). APT402, an apyrase-annexin V fusion protein, reduced arterial thrombus weight by 95% compared to placebo in a rabbit model without increasing bleeding time.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: