U.S. Renal Care Presents Analysis of VOICE Trial Demonstrating Favorable Safety Outcomes for Patients Treated with Vadadustat Versus an ESA During a Late-Breaking Session at American Society of Nephrology Kidney Week

Vadadustat shows lower hospitalization and better hemoglobin control than ESA in dialysis patients.

What the company is saying

Akebia Therapeutics highlights new VOICE trial data presented by U.S. Renal Care at ASN Kidney Week 2026, positioning vadadustat (Vafseo) as a safer and more effective alternative to erythropoiesis-stimulating agents (ESA) for anemia in chronic kidney disease patients on dialysis. The announcement emphasizes statistically significant reductions in hospitalization rates and improved hemoglobin stability with vadadustat, while also noting fewer serious adverse events. Geoffrey A. Block, M.D., FASN, Associate Chief Medical Officer and Senior Vice President, Clinical Research & Medical Affairs for USRC, is quoted to reinforce the clinical significance and potential for vadadustat to become a new standard of care. The company stresses that Vafseo is the only oral HIF-PHI approved for anemia in the U.S. and is available in 37 countries. Safety warnings and adverse event rates are disclosed in detail, reflecting a balanced tone that acknowledges both efficacy and risks. The narrative is confident, grounded in realized clinical outcomes, and avoids overstatement.

What the data suggests

The VOICE trial enrolled 2,116 patients and demonstrated a win odds of 1.16 (95% CI 1.06, 1.28, p=0.0016) for the primary composite endpoint of all-cause mortality and hospitalization, establishing both non-inferiority and superiority for vadadustat versus ESA. Hospitalization rates were 10% lower with vadadustat (111.1 vs. 123.1 hospitalizations per 100 patient-years; incidence rate ratio 0.90, 95% CI 0.82–0.99). Mortality rates were identical at 8.8% per 100 patient-years for both groups (incidence rate ratio 1.00, 95% CI 0.72–1.39). Serious adverse events were lower with vadadustat (121.5 vs. 134.2 events per 100 patient-years). Vadadustat reduced the odds of high hemoglobin excursions by 64% for levels above 12 g/dL (29.6% vs. 51.2%), 57% for above 13 g/dL (6.4% vs. 12.7%), and 61% for above 14 g/dL (1.6% vs. 3.2%). The odds of requiring ESA rescue were 28% lower with vadadustat (44.6% vs. 52.8%). Adverse reactions included hypertension (14% vadadustat, 17% darbepoetin alfa), serious hypertension (2.7% vs. 3%), seizures (1.6% both), GI erosions (6.4% vs. 5.3%), serious GI erosions (3.4% vs. 3.3%), and malignancies (2.2% vs. 3.0%). Vafseo is approved in 37 countries and has been available in the U.S. since January 2025. The data are comprehensive, statistically robust, and directly support the claims of improved safety and hemoglobin control.

Analysis

The announcement is grounded in realised, statistically robust clinical trial results from the VOICE study, with detailed numerical data on efficacy and safety endpoints for vadadustat versus ESA. The majority of claims are factual and supported by disclosed trial outcomes, including hospitalization rates, adverse events, and hemoglobin control, as well as regulatory approval milestones (FDA approval in March 2024, commercial availability since January 2025). Only a small fraction of the language is forward-looking, limited to general beliefs about vadadustat's potential to become a new standard of care. There is no evidence of exaggerated tone or narrative inflation; the language is proportionate to the data presented. No large capital outlay or long-dated, uncertain returns are discussed. The absence of financial metrics is not a deficiency here, as this is a clinical and regulatory update for an already-approved product.

Risk flags

• ●Despite improved hospitalization and hemoglobin control, vadadustat carries significant safety warnings, including increased risks of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access, particularly if hemoglobin is targeted above 11 g/dL. These risks are highlighted in the boxed warning and require careful dosing and monitoring.
• ●Hepatocellular injury, though rare (less than 1% of patients), necessitates regular monitoring of liver function (ALT, AST, bilirubin), with 1.8% of patients experiencing elevated liver enzymes and 0.3% elevated bilirubin. This could limit use in patients with pre-existing liver disease.
• ●Hypertension and serious worsening of hypertension were reported in 14% and 2.7% of vadadustat patients, respectively, requiring ongoing blood pressure management and monitoring. Cases of hypertensive crisis, including encephalopathy and seizures, have also been reported.
• ●Vadadustat is not recommended for patients with cirrhosis, active liver disease, or those not on dialysis, and has shown increased risks in non-dialysis CKD populations in prior studies. This restricts the eligible patient population and limits broader commercial uptake.
• ●Long-term malignancy risk remains uncertain, with 2.2% of vadadustat patients developing malignancies compared to 3.0% with darbepoetin alfa, and the product is not recommended in patients with active malignancies. Ongoing surveillance is needed.

Bottom line

Akebia Therapeutics' vadadustat (Vafseo) has demonstrated statistically significant clinical advantages over ESA in reducing hospitalization rates and improving hemoglobin control in dialysis-dependent chronic kidney disease patients, as shown in a large, randomized trial of 2,116 patients. The product is already FDA-approved and commercially available in the U.S. and 36 other countries, making these benefits immediately accessible to eligible patients. Safety risks, including cardiovascular events, liver injury, hypertension, and malignancy, are clearly disclosed and will require ongoing monitoring and careful patient selection. The data are robust and directly support the company's claims, but commercial success will depend on physician adoption within the defined patient population and continued post-market safety surveillance. Investors should focus on future disclosures of market uptake, revenue, and real-world safety outcomes to assess the financial impact. The most important takeaway is that vadadustat is now a clinically validated, available alternative to ESA for anemia in dialysis patients, with a differentiated safety and efficacy profile.

Announcement summary

(NASDAQ:AKBA) Akebia Therapeutics, Inc. announced that U.S. Renal Care (USRC) presented data from the Vafseo Outcomes In Center Experience (VOICE) trial at ASN Kidney Week 2026, highlighting significantly improved safety outcomes in patients treated with vadadustat compared to an erythropoiesis-stimulating agent (ESA). The VOICE trial enrolled 2,116 patients and was a randomized, open-label, active-controlled, noninferiority trial sponsored by USRC to measure the safety of vadadustat administered three times weekly versus standard-of-care ESA, using a hierarchical composite endpoint of mortality and hospitalization rates. The trial demonstrated a win odds of 1.16 (95% CI 1.06, 1.28, p=0.0016), establishing non-inferiority and superiority of the primary composite endpoint. The hospitalization rate was 10% lower in patients treated with vadadustat versus ESA, with 111.1 versus 123.1 hospitalizations per 100 patient-years and an incidence rate ratio of 0.90 (95% CI, 0.82, 0.99). There was no statistically significant difference between mortality rates with vadadustat versus ESA (8.8% versus 8.8% per 100 patient-years, incidence rate ratio of 1.00 (95% CI 0.72, 1.39)). Exposure-adjusted serious adverse events were lower with vadadustat (121.5 events per 100 patient-years) compared to ESA (134.2 events per 100 patient-years). Vadadustat improved hemoglobin control versus ESA, with a 64% reduction in the odds of a hemoglobin above 12 g/dL (29.6% vs. 51.2%, p<0.0001), a 57% reduction in the odds of a hemoglobin above 13 g/dL (6.4% vs. 12.7%, p<0.0001), and a 61% reduction in the odds of a hemoglobin above 14 g/dL (1.6% vs. 3.2%, p=0.0044). There was no overall difference in low hemoglobin excursions (below 9, 8, or 7 g/dL). The odds of ESA rescue were 28% less likely with vadadustat versus ESA (44.6% vs. 52.8%, p=0.0006). Vafseo (vadadustat) was approved by the U.S. FDA in March 2024 for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least three months and has been available in the U.S. since January 2025. Vafseo is approved for once-daily administration and is the only oral HIF-PHI for anemia in the U.S. market or in development. U.S. Renal Care partners with nephrologists to care for more than 37,000 people living with kidney disease across 32 states. Vafseo is approved for use in 37 countries. The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea. Hepatocellular injury attributed to Vafseo was reported in less than 1% of patients, with elevated serum ALT, AST, and bilirubin levels observed in 1.8%, 1.8%, and 0.3% of CKD patients treated with Vafseo, respectively. Worsening of hypertension was reported in 14% of Vafseo and 17% of darbepoetin alfa patients, with serious worsening in 2.7% of Vafseo and 3% of darbepoetin alfa patients. Seizures occurred in 1.6% of Vafseo and 1.6% of darbepoetin alfa patients. Gastric or esophageal erosions occurred in 6.4% of Vafseo and 5.3% of darbepoetin alfa patients, with serious GI erosions in 3.4% of Vafseo and 3.3% of darbepoetin alfa patients. Malignancies were observed in 2.2% of Vafseo and 3.0% of darbepoetin alfa patients. Vafseo is not recommended in patients with cirrhosis or active, acute liver disease.

Disagree with this article?