Mar 28, 2024   SOURCE: PR NewsWire

Vafseo® approved by the U.S. FDA for the treatment of anemia due to chronic kidney disease in dialysis-dependent adult patients

ST. GALLEN, SWITZERLAND, March 28, 2024 /PRNewswire/ -- CSL Vifor is pleased that its partner Akebia Therapeutics, Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved Vafseo (vadadustat) tablets for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. Vafseo is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) developed by Akebia.

"We congratulate our partner Akebia on the FDA approval, which represents an important moment in our shared efforts toward improving the lives of dialysis patients with anemia due to CKD in the U.S.," said Hervé Gisserot, General Manager of CSL Vifor. "As we continue to deliver on our promise for patients and public health, we are eager to closely collaborate with our partners to make this new oral treatment option available to patients."

"Patients receiving maintenance dialysis would benefit from additional therapeutic options that can effectively increase and maintain hemoglobin concentrations within guideline-recommended target ranges," said Glenn M. Chertow, M.D., M.P.H., Professor of Medicine, Division of Nephrology at Stanford University and Co-Chair of the independent Executive Steering Committee for PRO(2)TECT and INNO(2)VATE, the global Phase 3 clinical development programs for Vafseo.

The approval of Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months is based on efficacy and safety data from the INNO(2)VATE program and an assessment of post marketing safety data from Japan where Vafseo was launched in August 2020. Results from the INNO(2)VATE program were published in the New England Journal of Medicine: (N Engl J Med 2021; 384:1601-1612); (N Engl J Med 2021; 384:1589-1600). See the Important Safety Information section below, including BOXED WARNING regarding increased risk of death, myocardial infarction, stroke, venous thromboembolism and thrombosis of vascular access.

CSL Vifor has been granted an exclusive license to sell Vafseo to Fresenius Kidney Care dialysis centers and specific other third-party dialysis organizations in the U.S., allowing us to potentially reach approximately 60% of the dialysis patients in the country.

About CSL Vifor

CSL Vifor is a global partner of choice for pharmaceuticals and innovative, leading therapies in iron deficiency and nephrology. We specialize in strategic global partnering, in-licensing and developing, manufacturing and marketing pharmaceutical products for precision healthcare, aiming to help patients around the world lead better, healthier lives. Headquartered in St. Gallen, Switzerland, CSL Vifor also includes the joint company Vifor Fresenius Medical Care Renal Pharma (with Fresenius Medical Care).

The parent company, CSL (ASX: CSL; USOTC: CSLLY), headquartered in Melbourne, Australia, employs 32,000 people and delivers its lifesaving therapies to people in more than 100 countries. For more information about CSL Vifor, visit www.cslvifor.com.

About anemia due to chronic kidney disease (CKD)

Anemia is a condition in which a person lacks enough healthy red blood cells to carry adequate oxygen to the body's tissues. It commonly occurs in people with CKD because their kidneys do not produce enough erythropoietin, a hormone that helps regulate production of red blood cells. Anemia due to CKD can have a profound impact on a person's quality of life(1) as it can cause fatigue, dizziness, shortness of breath and cognitive dysfunction. Left untreated, anemia leads to deterioration in health and is associated with increased morbidity and mortality(2) in people with CKD.

Approximately 500,000 adult patients in the U.S. on dialysis suffer from anemia due to CKD(3), which may be associated with many adverse clinical outcomes. The burden of managing uncontrolled anemia in CKD patients can be substantial, both in terms of healthcare costs and the impact on patients, healthcare providers and caregivers. Today, most CKD patients are treated for anemia with injectable erythropoiesis-stimulating agents mostly administered at dialysis centers.

About Vafseo(®) (vadadustat)

Vafseo 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.


            
              See full prescribing information for complete boxed warning.



            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 AccessA 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 month
        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 VASFEO, 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.



    --  HepatotoxicityHepatocellular 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.



    --  HypertensionWorsening 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.



    --  SeizuresSeizures 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 ErosionGastric 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 DialysisThe 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.

    --  MalignancyVAFSEO 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.

References:

(1 )Eriksson D, et al. BMC Nephrol. 2016;17:97; Finkelstein FO, et al. Clin J Am Soc Nephrol. 2009;4:33-38; Farag YM, et al. Clin Nephrol. 2011;75:524-533

(2 )Portolés J, et al. BMC Nephrol. 2013;14:2. 3. NICE. Clinical Guideline: Anaemia Management in Chronic Kidney Disease: Partial Update 2015. 4. Silverberg DS, et al. Clin Lab Haematol. 2001;23:1-6. 5. Herzog CA, et al. J Card Fail. 2004;10:467-472

(3) United States Renal Data System. 2022 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2022; Dopps.org.

CSL Vifor Media Contact
Thomas Hutter

+41 79 957 96 73
media@viforpharma.com

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