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Abstract: PO0463

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

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Parfrey, Patrick S., Memorial University of Newfoundland, St. John's, Newfoundland, Canada
  • Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Maroni, Brad, 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
  • McCullough, Peter A., Baylor University Medical Center at Dallas, Dallas, Texas, United States
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) noninferiority trials (INNO2VATE) compared the safety and efficacy of VADA with that of darbepoetin alfa (DA) in adult patients with dialysis-dependent (DD) CKD. One trial randomized 369 patients with incident DD-CKD (Correction/Conversion trial; NCT02865850) and the other trial randomized 3544 patients with prevalent DD-CKD (Conversion trial; NCT02892149). The primary safety endpoint of the INNO2VATE 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 pooled MACE risk (hazard ratio [HR]; VADA:DA) was similar between the VADA and DA groups (0.96; 95% confidence interval [CI], 0.83–1.11), which met 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 1947 patients received VADA and 1955 received DA in the 2 studies. A first thromboembolic event occurred in 169 patients (8.7%) in the VADA group and 148 (7.6%) in the DA group (HR [95% CI]: 1.20 [0.959–1.493]; P value of Gray’s test=0.161). For arterial thrombosis, DVT, or PE, the number of patients with events was 26 (1.3%) and 32 (1.6%), respectively (HR [95% CI]: 0.86 [0.509–1.444]; P=0.462), and for venous thromboembolic events, there were 19 (1.0%) and 28 (1.4%), respectively (HR [95% CI]: 0.71 [0.400–1.269]; P=0.206). Vascular-access thrombosis was reported as 6.6 events/100 patient years in both the VADA and DA groups.

Conclusion

In the phase 3 INNO2VATE trial in patients with anemia and DD-CKD, the rate of thromboembolic events was similar between the VADA and DA groups.

Funding

  • Commercial Support