Merck – known as MSD outside the US and Canada – has received fast track designation from the US Food and Drug Administration (FDA) for MK-2060, an investigational anticoagulant therapy for the reduction of major thrombotic cardiovascular events in patients with end-stage renal disease (ESRD).
ESRD, also called end-stage kidney disease or kidney failure, occurs when chronic kidney disease — the gradual loss of kidney function — reaches an advanced state to the point that the kidneys can no longer function on their own.
While anticoagulants such as factor Xa inhibitors work well in lower-risk patients, there remains a need for treatments that can prevent blood clots in individuals who have higher bleeding risks.
Factor XI, however, is a protein in the blood which is transformed into its active enzyme form – factor XIa – as part of the blood coagulation cascade, and has been identified for potentially safer anticoagulant drugs as factor XI deficiency or inhibition is associated with little or no bleeding.
MK-2060 is a novel inhibitor of factor XI, administered intravenously, and designed to work through a dual mechanism of action both blocking the activation of factor XI as well as the downstream activity of activated protein.
The therapy is currently being investigated in a phase 2 study to evaluate the efficacy and safety of two different doses of MK-2060 in participants with ESRD receiving haemodialysis via an arteriovenous graft (AVG).
Commenting on the FDA’s decision, Dr Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said: “At Merck we are focusing our efforts where the needs are greatest, and we believe we have a significant opportunity with MK-2060 for the potential prevention of thrombosis in patients with advanced forms of kidney disease.
“We are encouraged by this fast track designation because additional anticoagulation medicines are urgently needed for patients with ESRD who are susceptible to high rates of life-threatening thrombotic events as well as high bleeding risk. Today there is no anticoagulation standard of care for such patients.”
The company is not alone though in identifying factor XI as the future of anticoagulation. Bayer, for example, is trialling a factor XI antisense candidate – fesomersen – in collaboration with Ionis Pharmaceuticals in ESRD patients on haemodialysis