FDA Panel Finds Benefit of Daprodustat Outweighs Risk for Adult Dialysis Patients with Anemia of Chronic Kidney Disease

The FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) recently voted 13-3 that the advantage of treatment with daprodustat outweighs its risks for use in adult dialysis patients with anemia of chronic kidney disease (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.

The FDA will consider the vote, feedback, and recommendations by CRDAC during its review of the new drug application (NDA) but is not bound by the committee’s recommendation. The FDA accepted the NDA for daprodustat and assigned a Prescription Drug User Fee Act date of February 1, 2023.

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) belonging 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 is being 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.

“[The] robust discussion was an important step in the review of daprodustat. We are pleased the committee recognized the potential for daprodustat to help certain patients who are living with anemia of CKD given limited treatment options,” said Chris Corsico, senior vice president, Development, GSK, in a press release. “We want to thank the physicians, patients and advocacy community who shared their valuable insights about this disease. We look forward to continuing to work with the US FDA as they complete their review of our new drug application.”

REFERENCE

GSK reports outcome from US FDA Advisory Committee meeting on daprodustat for anaemia of CKD. GSK. October 27, 2022. Accessed October 28, 2022. https://www.gsk.com/en-gb/media/press-releases/gsk-reports-outcome-from-us-fda-advisory-committee-meeting-on-daprodustat-for-anaemia-of-ckd/