Revacept (soluble dimeric glycoprotein VI-Fc fusion protein) / advanceCOR - LARVOL DELTA

Plasma chemokines indicate enhanced bleeding in patients with chronic coronary syndrome undergoing percutaneous coronary stenting. (PubMed, Clin Res Cardiol) - "The composition of platelet-derived chemokines correlated with platelet functions following antiplatelet treatment. Thus, assessment of chemokines may offer the perspective to identify patients at increased risk for bleeding events. Likewise, modulation of platelet chemokines in patients with revacept treatment contributes to the efficacy of antiplatelet treatment and might attenuate pathophysiological cascades leading to haemorrhagic diathesis in patients with CAD."

Journal • Cardiovascular • Coronary Artery Disease • Thrombosis

GPVI as an effective antithrombotic target. (PubMed, Eur Heart J Cardiovasc Pharmacother) - "A range of specific GPVI inhibitors have been characterised and 2 of these inhibitors, glenzocimab and revacept, have completed phase II clinical trials in ischemic stroke. In this review, we summarise mechanisms of GPVI activation and the latest progress of clinically tested GPVI inhibitors, including their mechanisms of action. By focussing on what is known about GPVI activation, we also discuss whether alternate strategies could also be used to target GPVI."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Ischemic stroke • Thrombosis

Pharmacological Inhibition of Glycoprotein VI- and Integrin α2β1-Induced Thrombus Formation Modulated by the Collagen Type. (PubMed, Thromb Haemost) - " In this first comparison of four inhibitors of platelet-collagen interactions with antithrombotic potential, we find that at arterial shear rate: (1) the thrombus-inhibiting effect of Revacept was restricted to highly GPVI-activating surfaces; (2) 9O12-Fab consistently but partly inhibited thrombus size on all surfaces; (3) effects of GPVI-directed interventions were surpassed by Syk inhibition; and (4) α2β1-directed intervention with 6F1 mAb was strongest for collagens where Revacept and 9O12-Fab were limitedly effective. Our data hence reveal a distinct pharmacological profile for GPVI-binding competition (Revacept), GPVI receptor blockage (9O12-Fab), GPVI signaling (PRT-060318), and α2β1 blockage (6F1 mAb) in flow-dependent thrombus formation, depending on the platelet-activating potential of the collagen substrate. This work thus points to additive antithrombotic action mechanisms of the investigated drugs."

Journal • Cardiovascular • Thrombosis • SYK

Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial. (PubMed, Stroke) - P2 | "Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis."

Journal • P2 data • Cardiovascular • Ischemic stroke • Myocardial Infarction

Platelets, Thromboinflammation and Neurovascular Disease. (PubMed, Front Immunol) - "Furthermore, the clinical importance of neuroinflammatory mediators and a potential translational relevance of involved mechanisms are addressed also with focus on non-classical immune cells including microglia cells or platelets. As illustrative examples, novel agents such as Anfibatide or Revacept, which result in reduced recruitment and activation of platelets, a subsequently blunted activation of the coagulation cascade and further inflammatory process, demonstrating that mechanisms of neuroinflammation and thrombosis are interconnected and should be further subject to in depth clinical and basic research."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Multiple Sclerosis • Systemic Inflammatory Response Syndrome • Thrombosis

Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer. (PubMed, Sci Adv) - "Since GPVI is an antithrombotic target that does not impair hemostasis, it represents a safe cancer therapeutic. We propose that OTME-Chip could be deployed to study other vascular and hematological targets in cancer."

Biomarker • Journal • Tumor microenvironment • Hematological Disorders • Oncology • Ovarian Cancer • Solid Tumor

Dimers of the platelet collagen receptor Glycoprotein VI bind specifically to fibrin fibers during clot formation, but not to intact fibrinogen. (PubMed, J Thromb Haemost) - "We conclude that dimeric GPVI is the receptor for fibrin, exhibiting a similar K to those obtained for its binding to fibrinogen D-fragment and D-dimer, suggesting that fibrin(ogen)'s GPVI-binding site becomes exposed after fibrin formation or cleavage to fragment-D. Analysis of platelets bound to fibrin clots indicates that platelet GPVI binds to fibrin fibers comprising the clot."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial. (PubMed, JAMA Cardiol) - P2 | "There were few bleeding events and no significant differences between treatment arms. ClinicalTrials.gov Identifier: NCT03312855."

Clinical • Journal • P2 data • Cardiovascular • Coronary Artery Disease • Heart Failure

The antiplatelet agent revacept prevents the increase of systemic thromboxane A biosynthesis and neointima hyperplasia. (PubMed, Sci Rep) - "The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA and prevented the morphological and functional changes induced by platelets in CASMC. The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation."

Journal

Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction. (PubMed, Expert Opin Pharmacother) - "Identification of critical risk factors for IRI and targeting them individually rather than one size fits all approach should be the major focus of future research. Various newer therapies like tocilizumab, anakinra, colchicine, revacept, and therapies targeting the reperfusion injury salvage kinase pathway, survivor activating factor enhancement, mitochondrial pathways, and angiopoietin-like peptide 4 hold promise for the future."

Journal • Cardiovascular • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury

Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Artery Stenosis: Design and Rationale of a Randomized Phase II Clinical Trial. (PubMed, TH Open) - "The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis."

Clinical • Journal • P2 data • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Myocardial Infarction • MRI

Intracoronary Stenting and Antithrombotic Regimen: Lesion Platelet Adhesion as Selective Target of Endovenous Revacept (clinicaltrials.gov) - P2; N=334; Completed; Sponsor: Deutsches Herzzentrum Muenchen; Recruiting ➔ Completed

Clinical • Trial completion • Acute Coronary Syndrome • Cardiovascular • Coronary Artery Disease

Revacept, a Novel Inhibitor of Platelet Adhesion, in Patients Undergoing Elective PCI-Design and Rationale of the Randomized ISAR-PLASTER Trial. (PubMed, Thromb Haemost) - "A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept-a lesion-directed inhibitor of platelet adhesion-in patients undergoing elective PCI."

Clinical • Journal

Revacept, an Inhibitor of Platelet Adhesion in Patients With Symptomatic Carotid Artery Stenosis. Safety Data From the International Randomized Multicenter Revacept CS02 Phase 2 Study (ISC 2020) - "Coronary intervention was necessary in 1 patient (0.6%) and 5 patients (3.1%), 24 hours and 3 months after Revacept infusion, respectively. These complications rates are comparable to the rate at day 30 follow up within the ICSS-study: ischemic stroke (91 patients 5.3%), intracerebral hemorrhage (8 patients, 0.5%) and any wound hematoma (81 patients, 4.7%) Conclusions The addition of Revacept to guideline-recommended anti-thrombotic therapy in patients with symptomatic stenosis of the internal carotid artery did not increase bleeding complications within the overall study population compared to previous studies."

Clinical • P2 data

Revacept in Symptomatic Carotid Stenosis (Revacept/CS/02) (clinicaltrials.gov) - P2; N=158; Completed; Sponsor: AdvanceCor GmbH; Trial completion date: Oct 2018 ➔ Sep 2019

Clinical • Head-to-Head • Trial completion date

An update on novel antiplatelets in vascular patients. (PubMed, Curr Pharm Des) - "Vorapaxar remains the only novel antiplatelet that is approved for PAD. Other novel antiplatelets demonstrate positive results, but further studies focused on vascular patients are necessary. Novel experimental antiplatelets are still in early phases of the clinical and preclinical studies."

Clinical • Journal

Intracoronary Stenting and Antithrombotic Regimen: Lesion Platelet Adhesion as Selective Target of Endovenous Revacept (clinicaltrials.gov) - P2; N=332; Recruiting; Sponsor: Deutsches Herzzentrum Muenchen; Trial completion date: Jun 2019 ➔ May 2020; Trial primary completion date: May 2019 ➔ Mar 2020

Clinical • Trial completion date • Trial primary completion date

Revacept, an inhibitor of platelet adhesion in symptomatic carotid stenosis: Results from a phase II study (ESC 2019) - "There is a trend for increased anti-thrombotic and anti-ischemic potency with regard to clinical events. Final data will be presented at the congress."

P2 data

LMU Munich: platelet inhibition novel aspects on platelet inhibition and function. (PubMed, Clin Res Cardiol) - "in Thromb Haemost 117:1240-1248), done at 33 sites in Europe. Furthermore, besides other ongoing clinical studies, we initiated and are currently recruiting patients for the multi-centre randomized APixaban versus PhenpRocoumon in Patients With ACS and AF: APPROACH-ACS-AF study as well as for the multi-centre phase II randomized, double-blind, placebo-controlled study of revacept in Patients With Stable Coronary Artery Disease (Revacept/CAD/02) trial."

Journal • Review