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For adults with anemia due to chronic kidney disease (CKD) on dialysis for at least 3 months

Once-daily oral Vafseo: a HIF-PHI that controls hemoglobin (Hb) levels1,2

Icon representing EPO production in kidneys - Vafseo®
  • Stabilizes cellular HIF levels1
  • Stimulates the body's response to hypoxia1,3
  • Increases endogenous EPO production1,3
Explore the MOA
Icon for Vafseo® (vadadustat) clinical trials
  • Achieved and sustained target Hb levels (10 to 11 g/dL)1
  • Similar to an ESA* for cardiovascular outcomes1
See trial results
Icon signifying the oral dose of  Vafseo® (vadadustat)
  • Available as a once-daily oral tablet1
Read about dosing

EPO=erythropoietin; ESA=erythropoiesis-stimulating agent; HIF=hypoxia-inducible factor; HIF-PHI=hypoxia-inducible factor prolyl hydroxylase inhibitor; MOA=mechanism of action; PI=prescribing information.


*Darbepoetin alfa.


Trial Design1

The efficacy and safety of Vafseo given once daily for the treatment of anemia in adults with CKD on dialysis were demonstrated in 2 global, multi-center, randomized, active-controlled, non-inferiority, open-label trials (N=3923). Trial endpoints included the difference in mean change of Hb levels from baseline to primary evaluation period (Weeks 24 to 36) and secondary evaluation period (Weeks 40 to 52), and time to first occurrence of major adverse cardiovascular event (MACE), using pre-specified, non-inferiority margins between Vafseo and darbepoetin alfa for both endpoints.

View trial design

Vafseo is expected to be available for purchase in January 2025, through authorized specialty distributors once the Centers for Medicare & Medicaid Services grants a two-year Transitional Drug Add-on Payment Adjustment (TDAPA) period.

Talk to your dialysis organization leadership about Vafseo today.

efficacy

Vafseo stimulates the body’s physiologic response to achieve and sustain target Hb levels (10 to 11 g/dL)1,3

In both trials, Vafseo was non-inferior to an ESA (darbepoetin alfa) in correcting and maintaining Hb levels across geographic-specific target Hb ranges (10 to 11 g/dL in the US and 10 to 12 g/dL outside the US) in adults with dialysis-dependent CKD (DD-CKD) at Weeks 24 to 36 and Weeks 40 to 52.1

Efficacy results1

CI=confidence interval; LSM=least squares mean; SD=standard deviation.

safety

Vafseo demonstrated major adverse cardiovascular events (MACE) outcomes consistent with an ESA1

  • Vafseo was non-inferior to darbepoetin alfa in time to first occurrence of MACE in a pooled analysis of the Incident (INNO2VATE-1) and Prevalent (INNO2VATE-2) Dialysis Trials1
    • Non-inferiority of Vafseo was established because the upper bound of the 95% CI for the MACE hazard ratio was less than the pre-specified, non-inferiority margin of 1.25. The results were consistent for the individual components of the MACE endpoint


MACE in the INNO2VATE trials1 (ITT analyses†)


ITT=intent-to-treat ; PY=Person Years.

ITT analyses included events on and off treatment after randomization in patients who received at least one dose of study medication.

Adjusted for baseline covariates.


An analysis of the US region (N=2361 of 3902 total patients globally) for MACE and the individual MACE components, where patients were treated to a Hb target of 10 to 11 g/dL, showed a similar risk of MACE compared to darbepoetin alfa. The results were consistent for the individual components of the MACE endpoint.1

INNO2VATE: Analyses of the MACE endpoint and individual components for the US region where the adult patients were treated to a Hb target of 10 to 11 g/dL1


§Adjusted for baseline covariates.

Adverse reactions

The safety of Vafseo was evaluated in adults with anemia due to DD-CKD in the Incident (INNO2VATE-1) and Prevalent (INNO2VATE-2) Dialysis Trials. There were 1947 patients treated with Vafseo and 1955 treated with an ESA (darbepoetin alfa). In the Vafseo treatment arm, 71% were exposed for at least 6 months and 44% for at least 1 year.1

Adverse reactions (≥5%) in adult patients with DD-CKD during the Incident (INNO2VATE-1) and Prevalent (INNO2VATE-2) Dialysis Trials1

||Grouped terms:

Hypertension includes hypertensive crisis, pre-eclampsia, and hypertensive encephalopathy.

Headache includes occipital neuralgia.

Fatigue includes asthenia, lethargy, and malaise.

Vomiting includes hematemesis.

Gastrointestinal erosion includes duodenal ulcers and perforation, gastrointestinal ulcers, and perforation, esophageal ulcers and perforation, and unspecified site or hematemesis, gastrointestinal hemorrhage, Helicobacter duodenitis and gastritis, melena, and gastric hemorrhage.

Dizziness includes labyrinthitis, vertigo, vestibular neuronitis, and presyncope.

Dyspnea includes orthopnea and respiratory distress.


  • Permanent treatment discontinuation due to an adverse reaction was reported in 4.9% of patients treated with Vafseo and 1.1% of patients treated with darbepoetin alfa. Gastrointestinal symptoms (nausea, vomiting, and diarrhea) resulted in permanent treatment discontinuation in 1.8% of patients treated with Vafseo1

Adjudicated thrombotic vascular events in adult patients with DD-CKD (fatal and non-fatal events)

These data are not an adequate basis for comparison of rates between the study drug and active control.

#Based on time-to-first-event analysis.

mechanism
of action

Vafseo supports the body’s physiologic response to hypoxia, promoting endogenous EPO production1,3

dosing and administration

Vafseo is available as a convenient, once-daily oral tablet1

Assess

Prior to initiating Vafseo1:

  • Correct and rule out other causes of anemia and check iron levels
  • Measure Hb levels
  • Conduct liver testing

Administer

The recommended starting dose is 300 mg once daily1

Adjust

Adjust in 150-mg increments, between 150 mg and 600 mg, to achieve or maintain Hb levels within 10 to 11 g/dL1

Avoid

Avoid co-administering with phosphate binders or oral iron supplements as they may reduce the effectiveness of Vafseo1

Discuss with your patients a time to take Vafseo that works for them. Vafseo can be administered without regard to the timing or type of dialysis.1

  • Individualize dosing and use the lowest dose of Vafseo sufficient to reduce the need for red blood cell (RBC) transfusions. Do not target a Hb level higher than 11 g/dL1
  • The recommended starting dose is 300 mg orally once daily for patients being switched from an ESA and for patients not being treated with an ESA1
  • Administer Vafseo at least 1 hour before dosing oral iron supplements, products containing iron, or iron-containing phosphate binders1
  • Administer Vafseo at least 1 hour before, or 2 hours after, dosing non-iron-containing phosphate binders1
  • Vafseo should be swallowed whole. Tablets should not be cut, crushed, or chewed1

access


Product availability and reimbursement

Vafseo is expected to be available for purchase in January 2025, through authorized specialty distributors once the Centers for Medicare & Medicaid Services grants a two-year Transitional Drug Add-on Payment Adjustment (TDAPA) period.

Talk to your dialysis organization leadership about Vafseo today

Contact us icon Contact us

For Medical queries about Vafseo, please visit akebiamedical.com/contact-us

For all other queries, please contact AkebiaCares® at 1‑833‑4AKEBIA (425‑3242)

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.

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.

References: 1. Vafseo® [Package Insert]. Cambridge, MA: Akebia Therapeutics, Inc. 2. Eckardt KU, Agarwal R, Aswad A, et al. Safety and efficacy of vadadustat for anemia in patients undergoing dialysis. N Engl J Med. 2021;384(17):1601-1612. doi:10.1056/NEJMoa2025956 3. Gupta N, Wish JB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: a potential new treatment for anemia in patients with CKD. Am J Kidney Dis. 2017;69(6):815-826. doi:10.1053/j.ajkd.2016.12.011