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Abstract: PO0462

Assessment of Thromboembolic Events with Vadadustat vs. Darbepoetin Alfa for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • McCullough, Peter A., Baylor University Medical Center at Dallas, Dallas, Texas, United States
  • Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Anders, Robert, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Vargo, Dennis, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Parfrey, Patrick S., Memorial University of Newfoundland, St. John's, Newfoundland, Canada
Background

Vadadustat (VADA) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated for treatment of anemia due to chronic kidney disease (CKD). Two recently completed global phase 3, open-label, randomized (1:1), sponsor-blind, noninferiority trials (PRO2TECT) compared the safety and efficacy of VADA with that of darbepoetin alfa (DA) in adult patients with non–dialysis-dependent (NDD) CKD. One of the studies (NCT02648347) was in 1751 patients previously untreated with an erythropoiesis-stimulating agent (ESA). The other study (NCT02680574) was in 1725 ESA-treated patients. The primary safety endpoint of the PRO2TECT trials was time to first major adverse cardiovascular event (MACE; a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), prespecified as a pooled event-driven analysis of both trials. As previously reported, the hazard ratio (HR; VADA:DA) for MACE was 1.17 (95% confidence interval [CI], 1.01–1.36), which did not meet the prespecified noninferiority margin of 1.25.

Methods

Here we describe the prespecified pooled analysis of the secondary safety endpoints of time to first thromboembolic event, including (1) any thromboembolic event (a composite of events of vascular access thrombosis, arterial thrombosis, deep venous thrombosis [DVT], and pulmonary embolism [PE]), (2) arterial thrombosis, DVT, or PE, and (3) venous thromboembolic events (DVT or PE).

Results

A total of 1739 patients received VADA and 1732 received DA in these two studies. A first thromboembolic event occurred in 33 patients (1.9%) in the VADA group and 38 (2.2%) in the DA group (HR [95% CI]: 0.88 [0.554–1.408]; P value of Gray’s test=0.569). For arterial thrombosis, DVT, or PE, there were 21 (1.2%) and 25 (1.4%) patients with events, respectively (HR [95% CI]: 0.86 [0.480–1.544]; P=0.569), and for venous thromboembolic events, there were 18 (1.0%) and 23 (1.3%), respectively (HR [95% CI]: 0.80 [0.430–1.485]; P=0.445). Vascular-access thrombosis was reported as <1.0 event/100 patient years in both the VADA and DA groups.

Conclusion

In the phase 3 PRO2TECT trial in patients with anemia and NDD-CKD, the rate of thromboembolic events was similar between the VADA and DA groups.

Funding

  • Commercial Support –