Vadadustat: A New Option for Managing Anemia in Chronic Kidney Disease on Dialysis

Understanding Anemia in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) can significantly impact your body's ability to produce red blood cells. These red blood cells carry oxygen throughout your body, and when their production is low, you develop anemia. Symptoms of anemia can include fatigue, weakness, shortness of breath, cognitive dysfunction, and pale skin.

Healthy kidneys produce a hormone called erythropoietin (EPO) that stimulates the bone marrow to produce red blood cells.  However, in CKD, damaged kidneys struggle to produce enough EPO, leading to anemia.

Typically, one in seven individuals with kidney disease experiences anemia, and as the disease progresses, anemia becomes a more significant problem.

Traditional Treatment for Anemia in Dialysis Patients

For decades, the main treatment for anemia in dialysis patients has been injectable medications called erythropoiesis-stimulating agents (ESAs). These medications mimic the action of EPO, stimulating the bone marrow to produce more red blood cells.

While ESAs have been effective in managing anemia, some patients experience side effects, such as high blood pressure or an increased risk of blood clots.

Vadadustat (Vafseo): A New Oral Option Approved by the FDA

Vadadustat is a recently approved oral medication offering a new approach to managing anemia in adult patients with CKD on dialysis for at least 3 months. Vadadustat works differently from ESAs. Instead of mimicking EPO, it directly inhibits an enzyme called HIF prolyl hydroxylase. This enzyme normally targets a protein for degradation, but by inhibiting it, vadadustat allows the protein to accumulate. This protein then stimulates the body's natural EPO production, ultimately leading to increased red blood cell production.

The FDA approved vadadustat on March 27th, 2024, based on the results of two large clinical trials (INNO2VATE) involving almost 4,000 patients with CKD on dialysis. These trials compared vadadustat to darbepoetin alfa, a commonly used ESA medication. The results showed that vadadustat was as effective as darbepoetin alfa in raising and maintaining hemoglobin levels (the protein in red blood cells that carries oxygen). Additionally, vadadustat did not appear to increase the risk of blood clots compared to darbepoetin alfa.

The Food and Drug Administration (FDA) recently announced it has approved vadadustat (Vafseo, Akebia Therapeutics) to treat anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months. Approximately 500,000 adults who are on dialysis for CKD now have another treatment option with this once-daily tablet that can manage anemia.

Side Effects That May Occur

Vadadustat is a new medication, and long-term safety data is still being collected. While it is generally well-tolerated, some common side effects can occur. These include:

• High blood pressure
• Diarrhea
• Headache and dizziness
• Nausea and fatigue
• Abdominal pain and vomiting

There are very serious side effects that have occurred in a small percentage during trial testing: vascular access thrombosis (a problem with access to the vein for dialysis), myocardial infarction (heart attack), stroke, deep vein thrombosis, pulmonary embolism (a blood clot in the lungs).

Dosing

The recommended starting dose is 300 mg once a day. This is adjusted in increments of 150 mg to achieve or maintain Hb levels within 10 to 11 g/dL. Taking iron supplements may decrease the effectiveness of vadadustat.

Vadadustat is not a cure for CKD or anemia. It is a treatment to help manage the symptoms of anemia in dialysis patients. Therefore, regular blood tests are needed to monitor your hemoglobin levels and overall health while taking this new medication.

Sources: 

• Akebia Receives FDA Approval of Vafseo® (vadadustat) Tablets for the Treatment of Anemia due to Chronic Kidney Disease in Adult Patients on Dialysis
• Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis
• VAFSEO Prescribing information