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
PRO2TECT and INNO2VATE, 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 INNO2VATE
program and an assessment of post marketing safety data from
Japan where Vafseo was launched in
August 2020. Results from the
INNO2VATE 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 life1 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
mortality2 in people with CKD.
Approximately 500,000 adult patients in the U.S. on dialysis
suffer from anemia due to CKD3, 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 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 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.
- 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.
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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