Akebia Therapeutics Reports Positive Topline Data from VOCAL Trial Showing Vadadustat Dosed TIW Met Primary Endpoint of Non-Inferiority to ESA in Maintaining Hemoglobin

Trial results add to robust dataset comparing vadadustat to the current standard of care, including recent 2,100+ patient VOICE trial that demonstrated a clinically meaningful safety benefit

WALTHAM, Mass., Nov. 05, 2026 (GLOBE NEWSWIRE) -- Akebia Therapeutics^®, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, today announced topline results from VOCAL, an open-label trial to evaluate the efficacy and safety of three times per week (TIW) dosing of vadadustat compared to the current standard of care erythropoiesis-stimulating agents (ESA) in patients with anemia due to chronic kidney disease (CKD) receiving in-center hemodialysis. Vadadustat met the primary endpoint of non-inferiority to ESA in maintaining hemoglobin (Hb) and treatment-emergent serious adverse events rates were similar with vadadustat versus ESA.

Vafseo^® (vadadustat), was approved by the U.S. Food and Drug Administration in March 2024 for the treatment of anemia due to CKD 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.

The VOCAL results complement the clinical evidence on vadadustat and provide additional information about its investigational three-times weekly dosing regimen, including:

• Data from the VOICE trial of 2,116 patients demonstrated a statistically significant improved safety outcome in patients treated with vadadustat versus the ESA, Epogen, on the hierarchical composite endpoint of all-cause mortality and hospitalization, driven by a significant reduction in hospitalization rate.
• The prospective VOICE data analysis confirmed the post hoc win statistics analysis of the INNO₂VATE program in patients with dialysis-dependent (DD) CKD treated with vadadustat or the ESA, Aranesp, in which vadadustat demonstrated a statistically significant reduction on the composite endpoint of death and hospitalization rate versus ESA.
• The FO₂CUS trial demonstrated that vadadustat was non-inferior to the ESA, Mircera, in Hb control and serious adverse events rates were similar with vadadustat versus ESA when administered TIW to patients with DD-CKD.
  

“The VOCAL trial results add to the body of clinical evidence on vadadustat compared to various forms of ESA and provide additional information about its investigational three-times-weekly dosing regimen, which we believe is meaningful as dialysis providers and prescribers make care decisions,” said Steven K. Burke, M.D., Chief Medical Officer of Akebia. “We are grateful to the clinicians who participated in the trial and especially to the patients. We continue our commitment to bring innovation to people impacted by kidney disease.”

The VOCAL trial (ClinicalTrials.gov ID: NCT06901505) enrolled 353 patients across 18large dialysis organization hemodialysis clinics randomized (1:1) into vadadustat TIW or the ESA, Mircera. The primary efficacy endpoint was the mean change in Hb between baseline and the primary evaluation period (weeks 20-24). Vadadustat met the primary endpoint of non-inferiority to ESA. The least square mean difference in Hb was -0.45 g/dL (95% confidence interval -0.71, -0.19) for the comparison of the vadadustat group versus the ESA group. The lower bound of the 95% confidence interval was above the non-inferiority margin of –0.75 g/dL. The safety endpoint was the rate of treatment-emergent serious adverse events. Exposure-adjusted treatment-emergent serious adverse events rates were similar with vadadustat versus ESA. Patients treated with vadadustat experienced 159.7 events per 100 patient-years compared to 183.9 events per 100 patient-years for patients treated with ESA.

About Akebia Therapeutics
Akebia Therapeutics, Inc. is a fully integrated biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease. Akebia was founded in 2007 and is headquartered in Waltham, Massachusetts. For more information, please visit our website at www.akebia.com, which does not form a part of this release.

About Vafseo^® (vadadustat) tablets
Vafseo^® (vadadustat) tablets is a once-daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor that activates the physiologic response to hypoxia to stimulate endogenous production of erythropoietin, increasing hemoglobin and red blood cell production to manage anemia. Vafseo is approved for use in 37 countries.

INDICATION
VAFSEO is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months.

Limitations of Use

• VAFSEO has not been shown to improve quality of life, fatigue, or patient well-being.
• VAFSEO is not indicated for use:
  • As a substitute for red blood cell transfusions in patients who require immediate correction of anemia.
  • In patients with anemia due to CKD not on dialysis.

IMPORTANT SAFETY INFORMATION about VAFSEO (vadadustat) tablets

CONTRAINDICATIONS  

• Known hypersensitivity to VAFSEO or any of its components  
• Uncontrolled hypertension 

WARNINGS AND PRECAUTIONS

• Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular Access
  A rise in hemoglobin (Hb) levels greater than 1 g/dL over 2 weeks can increase these risks. Avoid   in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting VAFSEO. Targeting a Hb level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events. Use the lowest effective dose to reduce the need for red blood cell (RBC) transfusions. Adhere to dosing and Hb monitoring recommendations to avoid excessive erythropoiesis.

• Hepatotoxicity
  Hepatocellular injury attributed to VAFSEO was reported in less than 1% of patients, including one severe case with jaundice. Elevated serum ALT, AST, and bilirubin levels were observed in 1.8%, 1.8%, and 0.3% of CKD patients treated with VAFSEO, respectively. Measure ALT, AST, and bilirubin before treatment and monthly for the first 6 months, then as clinically indicated. Discontinue VAFSEO if ALT or AST is persistently elevated or accompanied by elevated bilirubin. Not recommended in patients with cirrhosis or active, acute liver disease.

• Hypertension
  Worsening of hypertension was reported in 14% of VAFSEO and 17% of darbepoetin alfa patients. Serious worsening of hypertension was reported in 2.7% of VAFSEO and 3% of darbepoetin alfa patients. Cases of hypertensive crisis, including hypertensive encephalopathy and seizures, have also been reported in patients receiving VAFSEO. Monitor blood pressure. Adjust anti-hypertensive therapy as needed.

• Seizures
  Seizures occurred in 1.6% of VAFSEO and 1.6% of darbepoetin alfa patients. Monitor for new- onset seizures, premonitory symptoms, or change in seizure frequency.

• Gastrointestinal (GI) Erosion
  Gastric or esophageal erosions occurred in 6.4% of VAFSEO and 5.3% of darbepoetin alfa patients. Serious GI erosions, including GI bleeding and the need for RBC transfusions, were reported in 3.4% of VAFSEO and 3.3% of darbepoetin alfa patients. Consider this risk in patients at increased risk of GI erosion. Advise patients about signs of erosions and GI bleeding and urge them to seek prompt medical care if present.

• Serious Adverse Reactions in Patients with Anemia Due to CKD and Not on Dialysis
  The safety of VAFSEO has not been established for the treatment of anemia due to CKD in adults not on dialysis and its use is not recommended in this setting. In large clinical trials in adults with anemia of CKD who were not on dialysis, an increased risk of mortality, stroke, MI, serious acute kidney injury, serious hepatic injury, and serious GI erosions was observed in patients treated with VAFSEO compared to darbepoetin alfa.

• Malignancy
  VAFSEO has not been studied and is not recommended in patients with active malignancies. Malignancies were observed in 2.2% of VAFSEO and 3.0% of darbepoetin alfa patients. No evidence of increased carcinogenicity was observed in animal studies.

ADVERSE REACTIONS

• The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea.
  

DRUG INTERACTIONS

• Iron supplements and iron-containing phosphate binders: Administer VAFSEO at least 1 hour before products containing iron.
• Non-iron-containing phosphate binders: Administer VAFSEO at least 1 hour before or 2 hours after non-iron-containing phosphate binders.

• BCRP substrates: Monitor for signs of substrate adverse reactions and consider dose reduction.
• Statins: Monitor for statin-related adverse reactions. Limit the daily dose of simvastatin to 20 mg and rosuvastatin to 5 mg.

USE IN SPECIFIC POPULATIONS

• Pregnancy: May cause fetal harm. A pregnancy exposure registry is available to monitor outcomes in women exposed to VAFSEO during pregnancy. Report pregnancies to 1-844-445-3799.
• Lactation: Breastfeeding not recommended until two days after the final dose.
• Hepatic Impairment: Not recommended in patients with cirrhosis or active, acute liver disease.
  

Please note that this information is not comprehensive. Please click here for the Full Prescribing Information, including BOXED WARNING and Medication Guide.

Forward-Looking Statements

Statements in this press release regarding Akebia Therapeutics, Inc.'s (“Akebia's”) strategy, plans, prospects, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, and include, but are not limited to: Akebia’s beliefs and expectations regarding the body of clinical evidence comparing vadadustat to various forms of ESA, and the extent to which such evidence, including the VOCAL trial results, will be meaningful to dialysis providers and prescribers; Akebia’s beliefs regarding the data from the VOICE trial, including that the data demonstrated clinically meaningful safety benefit; and Akebia’s commitment to bring innovation to people impacted by kidney disease.

The terms “intend,” “believe,” “plan,” “goal,” “potential,” “anticipate,” “estimate,” “target,” “predict,” “expect,” “future,” “may,” “will,” “could,” “continue,” derivatives of these words, and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to, risks associated with: the potential therapeutic benefits, safety profile, and effectiveness of vadadustat; risks and uncertainties related to Akebia’s ongoing and planned research and development activities, including initiating, conducting or completing preclinical studies and clinical trials and the timing of such preclinical studies and clinical trials; the results of Akebia’s preclinical studies and clinical trials, including that initial, preliminary, interim, or top-line results do not necessarily predict final results and remain subject to final verification that may result in the final data being materially different from the initial data previously published; preclinical, clinical or retrospective data, analyses or results may not be replicated in, or predictive of, results of future preclinical or clinical data, analyses or results, or that such analysis or results may not support further development of such product candidates; Akebia’s ability to initiate and enroll patients in its clinical trials; decisions made by health authorities, such as the FDA, with respect to regulatory filings and other interactions; the potential demand and market potential and acceptance of, as well as coverage and reimbursement related to Akebia’s commercial products, including estimates regarding the potential market opportunity; the competitive landscape for Akebia’s commercial products, including generic entrants and the timing thereof; Akebia’s ability to obtain and maintain patent protection on its products and product candidates, and to successfully defend these patents against third-party challenges; Akebia’s ability to attract and retain qualified personnel; Akebia's ability to achieve and maintain profitability and to maintain operating expenses consistent with its operating plan; Akebia’s revenue and that its financial results from prior periods may not be indicative of future results; Akebia’s ability to refinance its senior secured term loan on acceptable terms or at all; manufacturing, supply chain and quality matters and any recalls, write-downs, impairments or other related consequences or potential consequences; early termination of any of Akebia's collaborations; and changes in the geopolitical environment and uncertainty surrounding U.S. trade policy on tariffs. Other risks and uncertainties include those identified under the heading “Risk Factors” in Akebia's most recent Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC), and other filings that Akebia may make with the SEC in the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and, except as required by law, Akebia does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.

Akebia Therapeutics® and Vafseo® are registered trademarks of Akebia Therapeutics, Inc.

Akebia Therapeutics Contact

Mercedes Carrasco
mcarrasco@akebia.com