Akebia Therapeutics announced that the Journal of the American Society of Nephrology has published geographic-specific analyses from the vadadustat global phase 3 clinical program, revealing important differences in treatment outcomes between U.S. and international patient populations with chronic kidney disease-related anemia.
The published analyses examined pre-specified U.S. and non-U.S. patient subgroups from four phase 3 trials: two INNO2VATE trials in patients with dialysis-dependent chronic kidney disease (DD-CKD) and two PRO2TECT trials in patients with non-dialysis-dependent CKD (NDD-CKD). These open-label, randomized, noninferiority trials compared the safety and efficacy of vadadustat with darbepoetin alfa in adult patients with CKD-related anemia.
Key Findings Reveal Geographic Treatment Differences
The analyses demonstrated distinct outcomes based on patient location and dialysis status. Among patients with DD-CKD, safety and efficacy of vadadustat and darbepoetin alfa were similar both in the U.S. and outside the U.S. However, among the U.S. patient subgroup with NDD-CKD, while safety and efficacy outcomes were similar, the risk for major adverse cardiovascular events (MACE) with vadadustat was higher than darbepoetin alfa outside the United States.
Safety was measured by time to first MACE, while efficacy was assessed by mean change in hemoglobin levels. The article, titled "Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States," provides detailed analysis of these geographic variations.
Clinical Implications for U.S. Physicians
"Geographic-specific pre-specified analyses of the vadadustat global phase 3 clinical program are important data as physicians in the U.S. are making care decisions for patients with CKD-related anemia," said Steven K. Burke, M.D., Senior Vice President, Research & Development and Chief Medical Officer of Akebia. "The analyses reflect how regional differences in clinical trial patient baseline characteristics, hemoglobin targets, and access to health care services and other regional clinical practices can ultimately contribute to differing outcomes in a global trial."
Regulatory Status and Market Availability
Vafseo (vadadustat) received U.S. Food and Drug Administration approval in March 2024 for treating anemia due to chronic kidney disease in adults who have been receiving dialysis for at least three months. The drug has been commercially available in the U.S. since January 2025 and is approved for use in 37 countries globally.
Mechanism of Action and Safety Profile
Vadadustat is a once-daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor that activates the physiologic response to hypoxia to stimulate endogenous erythropoietin production, increasing hemoglobin and red blood cell production to manage anemia.
The drug carries a boxed warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Targeting hemoglobin levels greater than 11 g/dL is expected to further increase these risks. The most common adverse reactions occurring in at least 10% of patients were hypertension and diarrhea.
Study Background and Publication History
The full results of the vadadustat global clinical phase 3 program were previously published in the New England Journal of Medicine, covering both the INNO2VATE and PRO2TECT trial results. The current publication in JASN adds important geographic context to these findings, helping clinicians understand how regional factors may influence treatment decisions and outcomes in CKD-related anemia management.
