Elinogrel
Elinogrel (previously known as PRT060128) is a novel, potent and selective P2Y12 inhibitor that is available in both intravenous (IV) and oral formulation. Elinogrel is a direct-acting drug (unlike thienopyridines that are pro-drugs) and does not require metabolic activation. Also, another difference from thienopyridines is that the inhibition of P2Y12 platelet receptor is reversible. Specifically, elinogrel has been shown to compete directly with ADP for binding at the P2Y12 receptor, being the first among the novel, non-thienopyridine P2Y12 inhibitors with this peculiarity. Elinogrel’s half-life is approximately 12 hours and the compound is cleared to a similar extent through the kidney and the liver. Elinogrel has recently concluded the phase II program and is currently in early phase III experimental phase. The drug is currently not commercially available.
Phase II of Elinogrel
Elinogrel has been tested in 2 phase II studies, one in patients with STEMI and another in patients with stable CAD undergoing PCI.
The ERASE-MI trial was a phase IIa, dose-escalation study were 70 patients with STEMI undergoing primary PCI were randomized to elinogrel or placebo. The trial was prematurely terminated for administrative reasons. The incidence of bleeding events was infrequent and similar between all tested doses of elinogrel and placebo and also no differences in serious adverse events, laboratory values, or ST resolution were demonstrated between elinogrel and placebo.
The INNOVATE-PCI was a larger phase IIb trial, in which 652 patients with stable CAD undergoing PCI were randomized in a double-blind fashion to elinogrel or matching placebo with a triple dummy design. Patients were assigned to receive either clopidogrel 300/600 mg followed by 75mg once daily or elinogrel 80 or 120 mg IV followed by 100 mg or 150 mg of orally twice daily before PCI. Compared with clopidogrel, elinogrel achieved a more rapid and potent platelet inhibition with similar rate of bleeding (which were primarily observed at the PCI access site) and also similar rate of clinical and biological efficacy end-points. Elinogrel was well tolerated but an increased incidence of dyspnea and transaminase elevation was reported.
- Berger JS, Roe MT, Gibson CM, Kilaru R, Green CL, Melton L, Blankenship JD, Metzger DC, Granger CB, Gretler DD, Grines CL, Huber K, Zeymer U, Buszman P, Harrington RA, Armstrong PW (2009). "Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial". Am Heart J. 158 (6): 998–1004. PMID 19958867.
- Leonardi S, Rao SV, Harrington RA, Bhatt DL, Gibson CM, Roe MT, Kochman J, Huber K, Zeymer U, Madan M, Gretler DD, McClure MW, Paynter GE, Thompson V, Welsh RC (2010). "Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI)". Am Heart J. 160 (1): 65–72. PMID 20598974.