Revacept (PR-15, GPVI-Fc)

Platelet adhesion to arterial vascular lesions and plaques plays a key role in the complications of atherosclerosis leading to acute coronary syndromes and myocardial infarctions as well as ischemic cerebral stroke.

Revacept is a human Fc fusion protein, which prevents the local activation of platelets at sites of vascular injury, acting like a “vascular coating”. Efficacy studies showed that revacept resulted in significantly reduced thrombus formation at these sites. However, systemic hemostasis is not affected.

In a first in man study, all doses were well tolerated, no drug-related adverse events occurred, bleeding time was not prolonged. No bleeding complications nor platelet depletion (thrombopenia) were observed.

A current phase II study in patients with symptomatic carotid artery stenosis, TIA or stroke (NCT01645306) investigates micro-embolic signals in brain arteries (determined by ultrasound), clinical results, MRI tomography, and blood parameters (e. g. platelet aggregation). The anticipated patient recruitment has almost been achieved – so far, no relevant adverse effects have been observed. Due to the blinded study design, the analysis of efficacy will be done at the end of the trial.

A second investigator-initiated phase II clinical study in patients with coronary artery disease (NCT 03312855; EudraCT 2015-000686-32) has been initiated at the team of Prof. Adnan Kastrati, German Heart Center, Munich and the team of Prof. Steffen Massberg, Großhadern Clinic of the Ludwig-Maximilian University, and at further large clinical entities who cooperate within the German Center for Cardiovascular Diseases (DZHK). To this end, a diagnostic blood test has been developed, which allows for risk stratification of patients.


Fusion proteins with GPVI-Fc

The platelet inhibitory potential of GPVI-Fc was further increased by fusing it to the ecto-nucleotidase CD39 which inhibits local adenosine diphosphate (ADP) accumulation at vascular plaques, and hence to create a lesion-directed dual antiplatelet therapy. GPVI-CD39 effectively stimulated local ADP degradation, and led to a significantly increased inhibition of plaque-induced platelet thrombus formation under arterial flow conditions.