Promising fast subcutaneous administration and a quick and potent antiplatelet effect, here comes a novel glycoprotein IIb/IIa inhibitor called RUC-4. This novel drug was tested in the CELEBRATE-02 study, presented at EuroPCR 2021 and simultaneously published in EuroIntervention.
The mean platelet inhibition begins 15 minutes after injection and increases with each of the three tested doses (from 77.5% with the lowest dose to 91.7% with the highest dose; p = 0.002 for trend).
RUC-4 was well tolerated by the 27 patients who received the drug and the next phase 2b study, which would include about 1600 patients in Europe, is already scheduled.
A single dose of RUC-4 might be enough for pre-hospital administration in patients with ST-segment elevation myocardial infarction who will undergo programmed primary angioplasty.
While fast reperfusion is key in these patients, existing drugs have limitations.
On the one hand, oral P2Y12 receptor inhibitors have a delayed action onset and, on the other hand, venous glycoprotein IIb/IIa inhibitors are a problem before hospitalization and have a prolonged half-life.
This might be the advantage offered by RUC-4: it acts in 15 minutes and platelets go back to normal in two hours.
Three different doses of RUC-4 (0.075, 0.09, and 0.11 mg/kg) were tested in the CELEBRATE-02 trial in patients with an infarction scheduled for primary angioplasty.
The drug was administered as a single subcutaneous injection before angiography—heparin was administered during the procedure to reach an activated clotting time <200 seconds. Ninety-three percent of the population received aspirin and ticagrelor.
The primary endpoint was the number of patients with a platelet inhibition >80% within 15 minutes of injection. Fifty percent of platelets were functioning normally at two hours.
No patient receiving RUC-4 experienced thrombocytopenia (one of the worst adverse events from traditional glycoprotein inhibitors).
The two access-related major bleedings could be attributed to perforation of collateral branches of the radial artery by the guidewire when advancing without fluoroscopy control.
Original title: Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction.
Reference: Bor WL et al. EuroIntervention 2021;17-online publish-ahead-of-print May 2021. DOI: 10.4244/EIJ-D-21-00287.