FDA Approves Novel Therapy for CKD-Related Anemia

The FDA has approved Jesduvroq (daprodustat) for the once-a-day treatment of anemia due to chronic kidney disease (CKD) in adults on dialysis. Chronic kidney disease is characterized by progressive loss of kidney function and is a risk factor for cardiovascular disease. Anemia is a frequent complication of CKD and affects about 700 million patients worldwide, with an estimated one in seven patients also developing anemia. In the United States, about 810,000 patients have end-stage renal disease, of which 558,000 patients receive dialysis.

Developed by GSK, Jesduvroq is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). It works to increase production of erythropoietin (EPO), which stimulates production of hemoglobin and red blood cells.

A spokesperson for GSK said they are working to make Jesduvroq available as soon as possible. A wholesale acquisition cost has not yet been set for Jesduvroq. Because 87% of dialysis patients are on Medicare, GSK is in the process of submitting the required documentation with Centers for Medicare & Medicaid Services (CMS) to help ensure timely reimbursement and patient access to Jesduvroq. This is expected in the fourth quarter 2023/first quarter 2024 time frame.

“Anemia of CKD can be a debilitating condition that is challenging to manage. This news means that patients on dialysis who are living with anemia of CKD now have another treatment option to help manage their anemia,” LaVarne Burton, president and chief executive officer of the American Kidney Fund, said in a press release.

The approval is based on the results of the ASCEND-D trial, which were published in the New England Journal of Medicine in December 2021. The study compared Jesduvroq with Aranesp (darbepoetin alfa), and Jesduvroq demonstrated noninferiority based on mean change in hemoglobin. The label includes a boxed warning about the increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Jesduvroq increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE).

In October 2022, the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 13 to 3 to support the use of Jesduvroq for adult dialysis patients with anemia of chronic kidney disease. But the committee did not support its use in non-dialysis patients. The ASCEND-ND trial of non-dialysis patients found that hazard ratio of time to first the major adverse cardiovascular event was 1.03. (A hazard ratio above 1 indicates increased risk of harm.) Committee members indicated they were uncertain about the possibility of increased cardiovascular risks in the non-dialysis patient population.

Jesduvroq is currently approved in Japan as Duvroq for patients with renal anemia. In March 2022, the European Medicines Agency validated the marketing authorization application (MAA) for daprodustat, which is currently under review.