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Abstract: PO0461

Vadadustat, an Oral HIF-PHI, Is Not Associated with Increased Risk of Neoplasm in Patients with Anemia due to CKD

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism


  • Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Vargo, Dennis, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Solinsky, Christine, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States

Vadadustat (VADA) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates endogenous erythropoietin and red blood cell production. The downstream effects of the transcription of HIF-responsive genes prompted our investigation of the risk of malignancy in patients with chronic kidney disease (CKD) receiving VADA in four global phase 3 trials.


We examined reports of adverse events (AEs) and serious AEs (SAEs) suggestive of neoplasms according to Standardized MedDRA Queries (preferred terms [PTs]) from four phase 3, randomized, open-label trials evaluating VADA vs darbepoetin alfa (DA) in patients from the two dialysis-dependent (DD) and two non–dialysis-dependent (NDD) CKD (INNO2VATE and PRO2TECT, respectively) who received ≥1 dose of study drug. Patients with a history of active malignancy within two years prior to or during screening were excluded from the trials, except for those with treated basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, or cervical carcinoma in situ. Malignancies are reported here as events per 100 patient-years (PY).


In total, 3686 patients were exposed to VADA and 3687 to DA for a median of 56.7 wk (25%, 75th percentile range 31.9–91.7 wk) and 70.0 wk (39.9–102.1 wk); 54.6% and 64.2% patients were exposed for ≥52 wk and 18.9% and 24.1% for >104 wk, respectively. Malignancies in the VADA and DA treatment groups were 2.1 events/100 PY and 2.7 events/100 PY, respectively (relative risk [RR], 0.81; 95% confidence interval [CI], 0.64–1.03). Specifically, malignancies in patients with NDD-CKD were 2.7 vs 3.0 events/100 PY (RR, 0.89; 95% CI, 0.65–1.21), and in patients with DD-CKD were 1.5 vs 2.4 events/100 PY (RR, 0.72; 95% CI, 0.50–1.03), for VADA vs DA, respectively. In both studies, no pattern was observed for any specific type of malignancy, including renal cell carcinoma in patients with DD or NDD CKD.


VADA was not associated with an increased risk of neoplasms compared with DA in patients with anemia and CKD.


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