Selatogrel, a novel P2Y₁₂ inhibitor: a review of the pharmacology and clinical development

ABSTRACT

Introduction

Platelet P2Y₁₂ 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 P2Y₁₂ 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 P2Y₁₂ 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 P2Y₁₂ inhibitory effects with a larger therapeutic window compared to the oral P2Y₁₂ 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 P2Y₁₂ inhibition (i.e. cangrelor), although some aspects need to be further clarified, including side effects, how to switch to oral P2Y₁₂ inhibitor and the association with concomitant drugs.

KEYWORDS:

• Antiplatelet
• cangrelor
• P2Y₁₂ antagonists
• pretreatment
• selatogrel

Article Highlights

• Selatogrel is a novel, potent, reversible, subcutaneous P2Y₁₂-inhibitor characterized by rapid onset and offset of action.

• Selatogrel is intended for use in high-risk settings, such as acute coronary syndrome or percutaneous coronary interventions, where patients may be more vulnerable to thrombotic complications.

• The excretion route of selatogrel is mainly faecal rather than urinary, hence posing fewer problems than other drugs in patients with reduced kidney function.

• Due to its route of administration, selatogrel may offer advantages in the pre-hospital or peri-procedural setting, e.g. in unconscious or emergency patients who cannot assume oral drugs.

• Selatogrel could represent a viable alternative to intravenous P2Y₁₂-inhibition (i.e. cangrelor) with an easier administration.

This box summarizes key points contained in the article.

Declaration of interest

D Capodanno declares that he has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. D J Angiolillo declares that he has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNov and St Jude Medical. DJ Angiolillo also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, and Renal Guard Solutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received speaker honoraria from Bayer, AstraZeneca and SedanaMedical. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded