Akebia Initiates Vafseo® (vadadustat) Post-Marketing Study in Conjunction with Large Dialysis Organization

Rhea-AI Summary

Akebia Therapeutics (Nasdaq: AKBA) has launched the VOCAL trial, a post-marketing study for its FDA-approved anemia treatment Vafseo® (vadadustat). The study, conducted in partnership with DaVita clinics, will evaluate the benefits of three-times-weekly Vafseo dosing compared to standard erythropoiesis-stimulating agents (ESA) in dialysis patients.

The trial will enroll approximately 350 patients across 18 DaVita hemodialysis clinics for up to 33 weeks. The study includes a sub-study of 28 patients to analyze red blood cell quality. Primary endpoints focus on hemoglobin changes, while secondary endpoints include serious adverse events, target hemoglobin achievement, and RBC transfusion requirements.

Positive

• Partnership with major dialysis provider DaVita for post-marketing study
• Large-scale trial with 350 patients to evaluate potential additional benefits
• Investigation of three-times-weekly dosing could improve treatment convenience
• Sub-study focusing on RBC quality could demonstrate additional advantages over current standard of care

Negative

• Study results and potential benefits not guaranteed
• Extended trial duration of 33 weeks may delay findings

Insights

Pharmaceutical Clinical Researcher

Akebia's post-marketing VOCAL study could expand Vafseo's clinical profile, potentially increasing market share in the lucrative dialysis market.

Akebia's initiation of the VOCAL trial represents a strategic post-marketing effort to strengthen Vafseo's clinical positioning following its March 2024 FDA approval and January 2025 commercial launch. This open-label study will evaluate three-times-weekly dosing compared to standard erythropoiesis-stimulating agents (ESAs) across approximately 350 patients in 18 DaVita clinics.

The trial design is particularly notable for two reasons. First, it explores a convenient three-times-weekly dosing regimen that would align with typical hemodialysis schedules, potentially improving treatment adherence and reducing administrative burden. Second, the sub-study examining red blood cell quality could differentiate Vafseo from ESAs by establishing advantages beyond just hemoglobin correction.

Partnering with DaVita, one of the largest dialysis providers in the US, is strategically significant. Positive outcomes could facilitate faster adoption within DaVita's extensive network. The study's endpoints are comprehensive, measuring not only hemoglobin changes but also serious adverse events, achievement of target hemoglobin range, and reduction in transfusion requirements.

The investigation into red blood cell phenotypes is particularly innovative, as ESAs have been shown to produce red blood cells with suboptimal characteristics. If Vafseo demonstrates superior RBC quality metrics, it could provide a compelling clinical advantage over the entrenched ESA market leaders, potentially supporting premium pricing and expanded market share in the dialysis setting.

Healthcare Business Analyst

The VOCAL trial represents a calculated market penetration strategy for Akebia's Vafseo in the highly competitive and lucrative dialysis market. The timing is particularly strategic—commencing just 7 months after commercial launch—indicating Akebia's aggressive push to establish Vafseo as a preferred treatment option.

The partnership with DaVita is commercially significant. As one of the two dominant dialysis providers in the US (alongside Fresenius), DaVita serves approximately 37% of US dialysis patients. Establishing evidence specifically within DaVita's ecosystem could accelerate formulary adoption across their network.

The three-times-weekly dosing regimen being studied aligns perfectly with standard hemodialysis schedules (typically Monday-Wednesday-Friday or Tuesday-Thursday-Saturday), creating operational efficiencies for dialysis centers by enabling administration during regular dialysis sessions. This convenience factor could be a major competitive advantage in the institutional setting where workflow efficiency directly impacts profitability.

The sub-study on red blood cell quality could potentially identify meaningful clinical differentiators from ESAs, which represent a multi-billion dollar market. If successful, this could help Akebia justify premium pricing or preferred formulary status in an increasingly cost-conscious healthcare environment.

For context, anemia management in dialysis patients is a substantial market opportunity, with nearly all of the approximately 550,000 US dialysis patients requiring treatment. Establishing Vafseo as a preferred option, particularly through partnership with a major provider like DaVita, could significantly accelerate market penetration and revenue growth for Akebia.

VOCAL, an open-label active-controlled study, is being conducted at DaVita dialysis clinics to evaluate benefits of treating patients with Vafseo three times a week

CAMBRIDGE, Mass., Aug. 04, 2025 (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 the initiation of a post-marketing study to identify additional potential benefits of Vafseo® (vadadustat). The VOCAL trial, conducted within DaVita clinics, aims to generate data to evaluate the efficacy and safety of three times per week (TIW) dosing of vadadustat compared to standard of care erythropoiesis-stimulating agents (ESA) in patients with anemia of CKD receiving in-center hemodialysis.

“Our team and partners within the dialysis community share a commitment to improving patient care,” said Steven K. Burke, M.D., Chief Medical Officer of Akebia. “The VOCAL trial, conducted within DaVita clinics, enables us to continue building the body of evidence on the effectiveness of Vafseo when dosed three times a week as well as to understand the potential additional benefits of Vafseo treatment for anemia in CKD patients.”

The VOCAL trial is expected to enroll approximately 350 patients across 18 DaVita hemodialysis clinics. This open-label trial will employ 1:1 randomization. Patients will participate in the study for up to 33 weeks including screening, treatment and safety follow-up. The primary endpoint of the study is change in hemoglobin, and secondary endpoints include number of patients reporting treatment-emergent serious adverse events, proportion of patients within target hemoglobin range and proportion of patients receiving RBC transfusions, in each case, compared to ESA treatment.

The VOCAL trial will also include a sub-study of approximately 28 patients from three clinics who will have blood samples collected and analyzed over the course of a 6-month treatment period. One major factor contributing to the anemia of CKD patients is reduced red blood cell (RBC) quality. Working in consultation with Vitalant Research Institute, the intent of the sub-study is to better understand the impact of Vafseo on RBC phenotypes (e.g. deformability, resistance to oxidative stress, metabolomics) compared to ESA treatment. 

“DaVita is committed to be at the forefront of innovation by evaluating novel treatments that improve clinical practice and benefit patient care,” said Dr. Steven Brunelli, MD, MSCE, Vice President and Medical Director of DaVita Outcomes Research. “The VOCAL trial evaluates Vafseo as a potential new standard of care in a real-world setting and explores additional potential benefits for patients.”

Vafseo was approved by the U.S. Food and Drug Administration in March 2024 for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months, and the product became available in the U.S. in January 2025.

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 Cambridge, 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

WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS.

VAFSEO increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE).

Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels.

No trial has identified a hemoglobin target level, dose of VAFSEO, or dosing strategy that does not increase these risks.

Use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions.

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.
• 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, statements regarding: Akebia's expectations regarding the VOCAL trial, including expectations as to the potential benefits of Vafseo for the treatment of anemia in CKD patients, potential benefits of Vafseo when dosed three times a week and the expected patient enrollment; and Akebia’s beliefs and plans to establish Vafseo as the new standard of care for the treatment of anemia due to CKD. The terms "intend," "believe," "plan," "goal," "potential," "anticipate, "estimate," "expect," "future," "will," "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 Vafseo; the results of preclinical and clinical research; decisions made by health authorities, such as the FDA, with respect to regulatory filings and other interactions; the commercial availability of Vafseo; the potential demand and market potential and acceptance of, as well as coverage and reimbursement related to, Vafseo, including estimates regarding the potential market opportunity; the competitive landscape for Vafseo, including generic entrants and the timing thereof; the ability of Akebia to attract and retain qualified personnel; Akebia's ability to achieve and maintain profitability and to maintain operating expenses consistent with its operating plan; 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, and other filings that Akebia may make with the U.S. Securities and Exchange Commission 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

FAQ

What is the purpose of Akebia's VOCAL trial for Vafseo (AKBA)?

The VOCAL trial aims to evaluate the efficacy and safety of three-times-weekly Vafseo dosing compared to standard ESA treatment in dialysis patients, potentially identifying additional benefits of the medication.

How many patients will participate in Akebia's Vafseo VOCAL study?

The study will enroll approximately 350 patients across 18 DaVita hemodialysis clinics, with an additional sub-study of 28 patients for detailed blood analysis.

When was Vafseo approved by the FDA for dialysis patients?

Vafseo was approved by the FDA in March 2024 for treating anemia in adults with chronic kidney disease who have been on dialysis for at least three months.

What are the primary endpoints of the VOCAL trial for Vafseo?

The primary endpoint is change in hemoglobin levels. Secondary endpoints include treatment-emergent serious adverse events, proportion of patients within target hemoglobin range, and RBC transfusion requirements.

How long will patients participate in the Vafseo VOCAL trial?

Patients will participate in the study for up to 33 weeks, including screening, treatment, and safety follow-up periods.