Daprodustat, an investigational oral medication, is as effective as conventional therapy with erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD) in patients undergoing dialysis and those who are not, according to data from separate trials presented at the American Society of Nephrology’s Kidney Week 2021 and published concomitantly in the New England Journal of Medicine.

In addition, daprodustat was noninferior to ESA therapy with respect to cardiovascular safety, with no safety signals observed, according to investigators.

The findings are from 2 randomized open-label phase 3 trials led by Ajay K. Singh, MBBS, MBA, Senior Associate Dean for Postgraduate Medical Education at Harvard Medical School of Boston, Massachusetts, who presented data during a session titled “High-Impact Clinical Trials.”


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“Daprodustat could represent an oral alternative to ESA therapy for treating anemia of CKD in both dialysis and nondialysis patients,” Dr Singh told attendees.

In one trial, Dr Singh and colleagues randomly assigned 1487 patients undergoing dialysis to receive daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), and 1477 to receive an injectable ESA (epoetin alfa for those on hemodialysis and darbepoetin alfa for those on peritoneal dialysis). The mean change in hemoglobin from baseline to weeks 28 through 52 was 0.28 g/dL in the daprodustat recipients and 0.10 g/dL in the ESA group, a difference of 0.18 g/dL that met the prespecified noninferiority margin of -0.75 g/dL, Dr Singh reported.

During a median follow-up of 2.5 years, a major adverse cardiovascular event (MACE) occurred in 374 daprodustat recipients (25.2%) and 394 ESA-treated patients (26.7%), which also met the prespecified noninferiority margin for daprodutstat, according to the investigators.

In the other trial, the investigators randomly assigned 1937 patients with nondialysis CKD to receive daprodustat and 1935 to receive darbepoetin alfa. The mean baseline hemoglobin levels were similar in both groups. The mean change in hemoglobin level from baseline to weeks 28 through 52 was 0.74 g/dL for daprodustat recipients and 0.66 g/dL for those treated with darbepoetin alfa, a difference of 0.08 g/dL, which met the prespecified noninferiority margin of -0.75 g/dL.

During a median follow-up of 1.9 years, a first MACE occurred in 378 patients (19.5%) in the daprodustat group and 371 darbopoetin alfa recipients (19.2%), which met the prespecified noninferiority margin of 1.25, according to the investigators.

For both trials, investigators defined MACE as a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.

Disclosure: The trials were funded by GlaxoSmithKline, which is developing daprodustat.

References

Singh AK, Carroll K, Perkovic V, et al. ASCEND Program: Efficacy and safety from ASCEND-D and –ND and overall MACE finding. Presented at: Kidney Week 2021, November 2-7, 2021. Abstract: FR-OR66.

Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N Engl J Med. Published online November 5, 2021.

doi:10.1056/NEJMoa2113379

Singh AK, Carroll K, McMurray JJV, et al. Daprodustat for the treatment of anemia in patients not undergoing dialysis. N Engl J Med. Published online November 5, 2021. doi:10.1056/NEJMoa2113380