VOICE Trial Records 10% Lower Hospitalization With Vadadustat in Dialysis Patients

Key Facts

Akebia announced on October 26 results from an analysis of the VOICE trial presented by U.S. Renal Care during a late-breaking session at the American Society of Nephrology’s Kidney Week 2026. The analysis compared the safety of vadadustat, marketed as Vafseo, with standard ESA therapy in patients receiving in-center dialysis. The trial included 2,116 patients and used a randomized, open-label design with an active comparator. Participants received vadadustat three times weekly, while the comparator group received standard ESA therapy. The assessment focused on a hierarchical composite measure of mortality and hospitalization, rather than treatment efficacy as described in the previous draft. Akebia’s statement said the primary result showed noninferiority and superiority on the composite measure.

The win ratio on the composite measure was 1.16, with a 95% confidence interval between 1.06 and 1.28 and a p-value of 0.0016. The statement said this result met noninferiority and showed vadadustat’s superiority on the primary measure. Lower hospitalization was the most prominent component of the result: the rate was 111.1 events per 100 patient-years with vadadustat, compared with 123.1 events with ESA. That represents a 10% lower hospitalization rate in the vadadustat group. The incidence rate ratio was 0.90, with a 95% confidence interval between 0.82 and 0.99. The composite superiority was therefore driven by the hospitalization result, according to the figures reported in the company’s statement.

The analysis showed no statistically significant difference in mortality between the groups. The mortality rate was 8.8% per 100 patient-years with vadadustat, and the same rate with ESA. The incidence rate ratio was 1.00, with a 95% confidence interval between 0.72 and 1.39. This result sets a clear limit on what can be said about the composite measure: the statement reported superiority on the composite, but mortality alone did not differ statistically between the two treatments. The statement also reported exposure-adjusted rates of serious adverse events of 121.5 events per 100 patient-years with vadadustat, compared with 134.2 with ESA. These figures are part of the safety analysis presented at the session and do not change the separate mortality result.

The results also included measures related to hemoglobin control and the need for rescue treatment. The share of patients whose hemoglobin exceeded 12 g/dL was 29.6% with vadadustat, compared with 51.2% with ESA. The statement said the odds of exceeding this threshold fell 64% with vadadustat, with a p-value below 0.0001. The odds of resorting to ESA rescue were also 28% lower in the vadadustat group. In that group, 44.6% of patients used rescue treatment, compared with 52.8% in the comparator group, with a p-value of 0.0006. These additional measures support the picture of lower hospitalization in the analysis, while remaining separate from the mortality result.

The analysis comes in the context of an existing treatment: the U.S. Food and Drug Administration approved Vafseo on March 27, 2024, to treat anemia associated with chronic kidney disease in adults who have been on dialysis for at least three months. The original approval was based on two trials involving 3,923 adults with anemia associated with chronic kidney disease who were receiving dialysis. The FDA label carries a warning about the risks of death, heart attack, stroke, venous thromboembolism and vascular access thrombosis. It also warns that targeting a hemoglobin level above 11 g/dL is expected to increase the risks of death and arterial and venous thrombotic events. These warnings appear in the drug’s approved safety information and are not new findings from the VOICE trial.

Akebia expected to announce topline results from the VOCAL trial in the fourth quarter of 2026. VOCAL is studying vadadustat dosed three times weekly against ESA therapies, making it a separate clinical follow-up from the VOICE analysis. In the context of the company’s earlier data, Akebia said the interim VOICE analysis repeated safety results shown by a later statistical analysis of the INNO2VATE program. The results of that analysis were published in the Journal of the American Society of Nephrology, according to the company. At the close of the October 26 session, Akebia’s stock, AKBA, was about $0.6438. Available EL7 data do not include the session high and low prices.