The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for daprodustat for the treatment of patients with anemia of chronic kidney disease (CKD).

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. The NDA is supported by data from 5 ASCEND phase 3 clinical trials, which included the ASCEND-ND (ClinicalTrials.gov Identifier: NCT02876835) and ASCEND-D (ClinicalTrials.gov Identifier: NCT02879305) trials that evaluated the efficacy and safety of daprodustat in over 6000 patients with anemia of CKD who were not on dialysis or on dialysis, respectively.

Patients were randomly assigned to receive daprodustat or darbepoetin alfa in ASCEND-ND. For ASCEND-D, patients were randomly assigned to receive daprodustat or an erythropoietin-stimulating agent (ESA; [darbepoetin alfa or epoetin alfa]) from a standard of care therapy. The coprimary endpoints for both trials were the time to first occurrence of adjudicated major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke) during cardiovascular events follow-up time period, and the mean change in the hemoglobin level from baseline to weeks 28 through 52.

In the ASCEND-ND trial, results showed that patients in the daprodustat arm achieved a mean change in hemoglobin level of 0.74±0.02g/dL from baseline to weeks 28 through 52 compared with 0.66±0.02g/dL in the darbepoetin alfa arm (difference, 0.08g/dL; 95% CI, 0.03-0.13), which met the prespecified noninferiority margin of -0.75g/dL. Moreover, after a median follow-up of 1.9 years, MACE occurred in 19.5% (n=378/1937) of patients in the daprodustat arm compared with 19.2% (n=371/1935) of patients in the darbepoetin arm (hazard ratio [HR], 1.03; 95% CI, 0.89-1.19), which met the prespecified noninferiority margin. 

In the ASCEND-D trial, results showed that patients in the daprodustat arm achieved a mean change in hemoglobin level of 0.28±0.02g/dL from baseline to weeks 28 through 52 compared with 0.10±0.02g/dL in the ESA arm (difference, 0.18g/dL; 95% CI, 0.12-0.24), which met the prespecified noninferiority margin of -0.75g/dL. Moreover, after a median follow-up of 2.5 years, MACE occurred in 25.2% (n=374/1487) of patients in the daprodustat arm compared with 26.7% (n=394/1477) of patients in the ESA arm (HR, 0.93; 95% CI, 0.81-1.07), which met the prespecified noninferiority margin. 

A Prescription Drug User Fee Act (PDUFA) target date of February 1, 2023 has been set for this application.

References

  1. US Food and Drug Administration accepts New Drug Application for daprodustat. News release. GlaxoSmithKline plc. Accessed April 19, 2022. https://www.gsk.com/en-gb/media/press-releases/us-food-and-drug-administration-accepts-new-drug-application-for-daprodustat/
  2. Singh AK, Carroll K, McMurray JJ, et al. Daprodustat for the treatment of anemia in patients not undergoing dialysis. N Engl J Med. Published online December 16, 2021. doi: 10.1056/NEJMoa2113380
  3. Singh AK, Carroll K, McMurray JJ, et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N Engl J Med. Published online December 16, 2021. doi:10.1056/NEJMoa2113379