Selatogrel, a novel P2Y inhibitor: a review of the pharmacology and clinical development.

INTRODUCTION

Platelet P2Y inhibitors have a key role in reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) and those with acute coronary syndrome (ACS). Clopidogrel, prasugrel and ticagrelor are widely prescribed oral P2Y receptor antagonists, but numerous clinical and pharmacological factors can lead to impaired gastrointestinal absorption resulting in reduced antithrombotic protection. These observations underscore the need for novel compounds or routes of administration that enable more favorable pharmacokinetic and pharmacodynamic profiles while reducing the risk for thrombotic complications.

AREAS COVERED

Selatogrel, formerly known as ACT-246475, is a novel, potent, reversible, and selective non-thienopyridine antagonist of the P2Y receptor developed for subcutaneous administration. Results from preclinical, Phase 1 and 2 studies have shown selatogrel to have rapid absorption and sustained and reversible platelet P2Y inhibitory effects with a larger therapeutic window compared to the oral P2Y inhibitors. Such findings make selatogrel a promising agent to be tested in phase 3 studies.

EXPERT OPINION

Advantages of subcutaneous administration of selatogrel are fast onset of action, easy administration and the fecal excretion not requiring dose adjustment based on renal function. These characteristics may translate into an advantage in the peri-procedural setting and in emergency and/or unconscious patients. Selatogrel may represent a viable alternative to intravenous P2Y inhibition (i.e. cangrelor), although some aspects need to be further clarified, including side effects, how to switch to oral P2Y inhibitor and the association with concomitant drugs.