Vadadustat for Anemia in Patients Receiving Peritoneal Dialysis

Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia in chronic kidney disease (CKD). Results of INNO₂VATE studies, two recently completed global phase 3 trials in patients with dialysis-dependent CKD (DD-CKD), demonstrated the noninferiority of vadadustat to darbepoetin alfa for the primary safety end point of time to first major cardiovascular event (MACE: a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke) and the primary and secondary efficacy end points (correlation/maintenance of hemoglobin [Hb]).

During a virtual poster session at ASN Kidney Week 2021, Glenn M. Chertow, MD, MPH, and colleagues reported results of post hoc analysis of data from INNO₂VATE, the randomized (1:1), phase 3, global, open-label, sponsor-blind, parallel-group active controlled noninferiority trials that compared vadadustat to darbepoetin alfa to determine the safety and efficacy in patients with anemia of dd-CKD receiving either peritoneal dialysis or hemodialysis. The poster was titled Vadadustat for Treatment of Anemia in Patients with Dialysis-Dependent CKD Receiving Peritoneal Dialysis.

The prespecified primary safety end point was time to first MACE. The primary and key efficacy end point was the mean change in Hb from baseline to weeks 24 to 36. The key secondary efficacy end point was the mean change from baseline to weeks 40 to 52. The incidence of treatment-emergent adverse events was also examined.

A total of 3923 patients were randomized in the two INNO₂VATE trials. Of those, 309 were receiving peritoneal dialysis: 152 in the vadadustat arm and 157 in the darbepoetin alfa arm. Among the patients in the peritoneal dialysis population, the rates of MACE were similar in the vadadustat and darbepoetin alfa arms (25/152 [16.4%] and 27/157 [17.2%], respectively).

The least-squares mean difference in change in Hb from baseline was –0.10 g/dL (95% confidence interval [CI], –0.33 to 0.12) to weeks 24 to 36 and –0.19 g/dL (955 CI, –0.43 to 0.05) to weeks 40 to 52. The primary and key secondary efficacy end points met the prespecified noninferiority margin of ­–0.75 g/dL.

The incidence of overall treatment-emergent adverse events was 88.2% in the vadadustat arm versus 95.5% in the darbepoetin alfa arm. The overall incidence of serious adverse events was 52.6% in the vadadustat arm versus 73.2% in the darbepoetin alfa arm.

“Among patients receiving peritoneal dialysis in the INNO₂VATE phase 3 trials, safety and efficacy of vadadustat were comparable to darbepoetin alfa,” the researchers said.

Funding was provided by Akebia Therapeutics, Inc., and Otsuka Pharmaceuticals Development and Commercialization, Inc.

Source: Chertow GM, Boudville N, Chowdhury P. Vadadustat for treatment of anemia in patients with dialysis-dependent CKD receiving peritoneal dialysis. Abstract of a poster presented at the American Society of Nephrology virtual Kidney Week 2021 (Abstract PO0464), November 2021.