The Food and Drug Administration (FDA)’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 13 “yes”, 3 “no” on the question of whether the benefit of treatment with daprodustat outweighs the risks for adult dialysis patients with anemia of chronic kidney disease (CKD). The panel also voted 5 “yes”, 11 “no” on the question of whether the benefit of treatment with daprodustat outweighs the risk for adult nondialysis patients with anemia of CKD.

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. The New Drug Application was supported by data from five phase 3 clinical trials including the ASCEND-ND (ClinicalTrials.gov Identifier: NCT02876835) and ASCEND-D (ClinicalTrials.gov Identifier: NCT02879305) studies, which compared the efficacy and safety of daprodustat to darbepoetin alfa in over 6000 patients with anemia of CKD who were not on dialysis or on dialysis, respectively.

Results from both trials showed that daprodustat met the coprimary endpoints demonstrating the noninferiority to erythropoiesis-stimulating agents with respect to the mean change in hemoglobin level from baseline and the time to first occurrence of adjudicated major adverse cardiovascular events (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke).

While the trials met the coprimary endpoints, the panel noted that, “there were no other benefits demonstrated on how patients feel, function, or survive.” Moreover, in the ASCEND-ND study, a higher incidence of MACE (particularly in the US subgroup of patients and when analyzing cardiovascular death instead of all-cause mortality) and other cardiovascular endpoints (eg, thromboembolic disease, vascular access thrombosis) were reported with daprodustat compared with darbepoetin alfa. In both studies, hospitalizations for heart failure and gastrointestinal erosions/bleeding were observed with greater frequency in the daprodustat arm vs the darbepoetin alfa arm.

Although not bound by the committee’s recommendations, the FDA does take them into consideration when making decisions on approval. A Prescription Drug User Fee Act target date of February 1, 2023 has been set for the application.

References

  1. GSK reports outcome from US FDA Advisory Committee meeting on daprodustat for anaemia of CKD. News release. GSK plc. Accessed October 27, 2022. https://us.gsk.com/en-us/media/press-releases/gsk-reports-outcome-from-us-fda-advisory-committee-meeting-on-daprodustat-for-anaemia-of-ckd/
  2. FDA Briefing Document: NDA 216951. Drug name: Daprodustat. Cardiovascular and Renal Drugs Advisory Committee Meeting: October 26, 2022. https://www.fda.gov/media/162521/download