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

now approved

Once-daily oral Vafseo: the newest HIF-PHI that controls hemoglobin (Hb) levels^1,2

Stabilizes cellular HIF levels¹
Stimulates the body's response to hypoxia^1,3
Increases endogenous EPO production^1,3

Explore the MOA

Achieved and sustained target Hb levels (10 to 11 g/dL)¹
Similar to an ESA* for cardiovascular outcomes¹

See trial results

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

Download Large-Format PI

Download Medication Guide

Stay tuned! Vafseo will be available for purchase 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.

Design¹

Study treatments were administered for 52 weeks to assess the efficacy endpoints. After 52 weeks, patients continued on study medication to assess long-term safety until the event-driven MACE endpoints were reached.

Treatment¹

Patients were randomized 1:1 to either:

Vafseo at the starting dose of 300 mg once daily
- Vafseo was titrated in 150-mg increments, between 150 mg and 600 mg, to achieve the Hb target of 10 to 11 g/dL (US) or 10 to 12 g/dL (outside the US)
Darbepoetin alfa administered subcutaneously or intravenously as per prescribing information

Long-term, non-inferiority trials^1,2

Key inclusion criteria

Key exclusion criteria²

Patients were excluded if they had anemia that was considered to be due to causes other than CKD or if they had uncontrolled hypertension or had a recent cardiovascular event.

Clinical trial endpoints¹

Efficacy: Difference in mean change in Hb levels from baseline to primary evaluation period (Weeks 24 to 36)

An additional efficacy endpoint was the difference in mean change of Hb levels from baseline to the secondary evaluation period (Weeks 40 to 52)

Cardiovascular outcomes: Time to first occurrence of MACE

MACE was defined as all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke

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)^1¶

^¶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 production^1,3

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

Evaluation of anemia and iron stores¹

Correct and exclude other causes of anemia before initiation
Iron status should be evaluated before and during treatment. Administer supplemental iron therapy when serum ferritin is <100 mcg/L or when serum transferrin saturation is <20%. The majority of patients with CKD will require supplemental iron during the course of therapy
Measure Hb at baseline and as directed in the Vafseo PI

Liver testing¹

Assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin prior to the initiation of Vafseo

Important considerations¹

Taking into account the gradual rise in Hb with Vafseo, rescue therapy with RBC transfusion or ESA treatment may be considered if Hb levels fall below 9 g/dL or response is considered not acceptable
Patients receiving RBC transfusions are recommended to continue Vafseo during the transfusion period
Pause Vafseo for patients receiving ESA rescue and resume when Hb levels are ≥10 g/dL
Depending on the ESA, the pause in Vafseo treatment should be extended to:
- 2 days after the last dose of epoetin
- 7 days after the last dose of darbepoetin alfa
- 14 days after the last dose of methoxypolyethylene glycol-epoetin beta
Following ESA rescue, resume Vafseo at the prior dose or with a dose that is 150 mg greater than prior dose with subsequent titration according to the Vafseo PI

Dose titration¹

Do not increase the dose more frequently than once every 4 weeks
Decreases in dose can occur more frequently
Consider the patient’s clinical condition, Hb variability, Hb rate of incline/decline, and Vafseo responsiveness when adjusting the dose
A single Hb excursion may not require a dosing change:
- If the Hb rises rapidly (eg, more than 1 g/dL in any 2-week period or more than 2 g/dL in 4 weeks), interrupt or reduce the dose
- If the Hb level exceeds 11 g/dL, interrupt the dose of Vafseo until Hb is less than or equal to 11 g/dL, then resume with dose that is 150 mg less than the dose prior to interruption
- Treatment with Vafseo should not be continued beyond 24 weeks of therapy if a clinically meaningful increase in Hb level is not achieved. Alternative explanations for an inadequate response should be sought and treated before restarting therapy

Monitoring response to therapy¹

ULN=upper limit of normal.

access

Product availability and reimbursement

Talk to your dialysis organization leadership about Vafseo today

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, 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 use in patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting VAFSEO. Targeting a Hb level of greater than 11g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with ESAs, which also increase erythropoietin levels. No specific Hb target level, dose of VAFSEO, or dosing strategy has been identified to avoid these risks. Use the lowest effective dose and adhere to dosing and Hb monitoring recommendations to avoid excessive erythropoiesis.

Advise patients to seek immediate medical attention if they develop signs or symptoms of myocardial infarction, stroke, venous thromboembolism, or thrombosis of vascular access. Evaluate and manage promptly if these occur.

Hepatotoxicity

Hepatocellular injury attributed to VAFSEO was reported in less than 1% of patients, including one severe case with jaundice. All events were asymptomatic and resolved after discontinuation of VAFSEO. The time to onset was generally within the first 3 months of treatment. 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% (9.4 per 100 person-years [PY]) of patients receiving VAFSEO and 17% (11.8 per 100 PY) of patients receiving darbepoetin alfa. Serious worsening of hypertension was reported in 2.7% (1.7 per 100 PY) of patients receiving VAFSEO and 3% (1.8 per 100 PY) of patients receiving darbepoetin alfa. 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% (1.0 per 100 PY) of patients who received VAFSEO and 1.6% (1.0 per 100 PY) of patients who received darbepoetin alfa. Following initiation of VAFSEO, monitor patients closely for premonitory neurologic symptoms. Monitor for new-onset seizures, premonitory symptoms, or change in seizure frequency.

Gastrointestinal Erosion

Gastric or esophageal erosions occurred in 6.4% (4.0 per 100 PY) of patients receiving VAFSEO and 5.3% (3.3 per 100 PY) of darbepoetin alfa-treated patients. Serious gastrointestinal (GI) erosions, including GI bleeding and the need for red blood cell transfusions were reported in 3.4% (2.1 per 100 PY) and 3.3% (2.0 per 100 PY) of those receiving VAFSEO and darbepoetin alfa, respectively. Consider the risk of GI erosion in high-risk patients, including those with a history of GI erosion, peptic ulcer disease, and tobacco or alcohol use.

Advise patients of the signs and symptoms of erosions and GI bleeding and urge them to seek prompt medical care if present.

Serious Adverse Reactions in Patients with Anemia Due to Chronic Kidney Disease 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, myocardial infarction, 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% (1.3 per 100 PY) of patients treated with VAFSEO and 3.0% (1.8 per 100 PY) of patients treated with darbepoetin alfa. 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 (20 mg) and rosuvastatin (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 for use 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

now approved

efficacy

Trial design

safety

mechanism of action

dosing and administration

Before starting treatment

Starting treatment

During treatment

access

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.

INDICATION

INDICATION AND IMPORTANT SAFETY INFORMATION about VAFSEO (vadadustat) tablets

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.

INDICATION

mechanism
of action

IMPORTANT SAFETY INFORMATION
about VAFSEO (vadadustat) tablets

IMPORTANT SAFETY INFORMATION
about VAFSEO (vadadustat) tablets