FDA Approves Daprodustat for Anemia From Chronic Kidney Disease in Adult Dialysis Patients

The FDA has approved daprodustat (Jesduvroq, GSK) for the once daily treatment of anemia caused by chronic kidney disease (CKD) in adults administered dialysis for at least 4 months. The oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) is the first drug to gain approval for the treatment of anemia in more than 30 years and the only HIF-PHI approved in the United States.

“Over the last several decades, there has been little innovation in anemia of CKD. We are proud to have developed Jesduvroq as a new oral treatment where there is a patient desire for more options,” said Tony Wood, president and chief scientific officer, GSK, in a press release.

In November, the FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 13-3 that the advantage of treatment with daprodustat outweighs its risks for use in adult dialysis patients with anemia of CKD. However, among adult non-dialysis patients with anemia of CKD, CRDAC voted 11-5 that the benefit of treatment with daprodustat does not outweigh the risks.

Daprodustat belongs to a novel class of oral drugs evaluated for the treatment of anemia of CKD in adult patients on and not on dialysis. Inhibiting oxygen-sending prolyl hydroxylase enzymes has been found to stabilize hypoxia-inducible factors and can lead to the transcription of erythropoietin and other genes involved in the correction of anemia, which is similar to the physiological effects that occur in the human body at high altitude, according to the investigators. The drug was developed to provide an oral treatment option for patients with anemia of CKD.

Daprodustat was analyzed in the ASCEND phase 3 clinical program, which included 5 pivotal trials that met their primary endpoints in assessing the efficacy and safety of daprodustat for the treatment of anemia across the spectrum of CKD. Results from the ASCEND-ND for non-dialysis CKD patients and ASCEND-D for dialysis patients were published in The New England Journal of Medicine in November 2021. The ASCEND program enrolled more than 8000 patients treated for up to 4.26 years to evaluate the safety and efficacy profile of daprodustat for the treatment of anemia of CKD across the disease spectrum.

ASCEND-ND included 3872 non-dialysis dependent patients with anemia of CKD who were either switched from the standard of care (ESA) or who were not currently receiving ESA to receive daprodustat or the ESA control. Iron management protocols were instituted across both arms of the trial. The trial found that daprodustat improved and/or maintained hemoglobin within the target level for the patient population. The primary safety analysis of the intention-to-treat (ITT) population found that daprodustat produced non-inferiority for major adverse events cardiovascular events (MACE) compared to ESA control.

ASCEND-D included 2964 dialysis patients with anemia of CKD who were switched to receive daprodustat or ESA control from a standard of care ESA therapy. A uniform iron management protocol was instituted across both arms of the trial. The study showed that daprodustat improved or maintained hemoglobin within target levels, whereas the primary safety analysis of the ITT population showed that daprodustat produced non-inferiority of MACE compared to ESA control.

“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,” said LaVarne Burton, president and chief executive officer, American Kidney Fund.

Reference

Jesduvroq (daprodustat) approved by US FDA for anaemia of chronic kidney disease in adults on dialysis. GSK. News release. February 1, 2023. https://www.gsk.com/en-gb/media/press-releases/jesduvroq-daprodustat-approved-by-us-fda-for-anaemia-of-chronic-kidney-disease-in-adults-on-dialysis/