From basic science to life-saving therapy: the rationale, and drug discovery efforts that led to the direct factor Xa inhibitor eliquis.

Over the past few decades, drug discovery directed at the treatment and prevention of thromboembolic diseases has been challenged by the need to balance robust efficacy with improved safety relative to the standard of care. To this end, the most impactful advance to date has been the discovery and development of oral factor Xa inhibitors. In this essay, a brief account of the program that culminated in the discovery of Eliquis (apixaban) and the commitment to identify a compound with an optimal profile are described.

First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects.

Aims: The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa inhibitor, in Japanese and non-Japanese healthy subjects.

Methods: This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study of 2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A used four doses (1.

Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model.

Objective: Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy.

Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.

The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk.