General Information

Jesduvroq (daprodustat) is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor.

Jesduvroq is specifically indicated for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months.

Jesduvroq is supplied as tablets for oral administration. 

Evaluation of Anemia and Iron Stores

• Prior to initiating Jesduvroq, correct and exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding). Evaluate the iron status in all patients before and during treatment with Jesduvroq . Administer supplemental iron therapy when serum ferritin is less than 100 mcg/mL or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of therapy.

Liver Testing

•  Assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin prior to initiation of JJesduvro. Repeat the liver tests if the patient develops signs or symptoms that could be consistent with liver disease during treatment with Jesduvroq.

Dosing Information:

• Individualize dosing and use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions. Do not target a hemoglobin higher than 11 g/dL.
• Jesduvroq can be taken with or without food, and without regard to concomitant administration of iron or phosphate binders.
• Jesduvroq should be swallowed whole. Tablets should not be cut, crushed, or chewed.
• Jesduvroq can be administered without regard to the timing or type of dialysis.
•  If a dose of Jesduvroq is missed, it should be taken as soon as possible, unless it is the same day as the next dose. In this case, the missed dose should be skipped, and the next dose taken at the usual time. Double-doses should not be taken to make-up for a missed dose.

Recommended Dosage and Administration:

Adults with Anemia Due to Chronic Kidney Disease Receiving Dialysis for at Least 4 Months:

Adults Not Being Treated with an ESA: 

• For adults not being treated with an ESA, the starting dose of Jesduvroq is based on the hemoglobin level as seen below. Dose modifications are needed for patients receiving concomitant treatment with a moderate CYP2C8 inhibitor or moderate hepatic impairment. See drug prescription label for these modifications.

 Adults Being Switched from an ESA:

• For adults being switched from an ESA to Jesduvroq, the starting dose is based on the dose regimen of the ESA at the time of substitution. See table below. Dose modifications are needed for patients receiving concomitant 5 treatment with a moderate CYP2C8 inhibitor or moderate hepatic impairment. See drug label.

Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks for the first month and then every 4 weeks thereafter. See drug prescription label for modifications.

Mechanism of Action 

Jesduvroq (daprodustat) is a reversible inhibitor of HIF-PH1, PH2 and PH3 (IC50 in the low nM range). This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, leading to increased transcription of the HIF-responsive genes, including erythropoietin.

Side Effects

Adverse effects associated with the use of Jesduvroq may include, but are not limited to, the following:

• hypertension
• thrombotic vascular events
• abdominal pain

The Jesduvroq drug label comes with e Black Box Warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access. Jesduvroq 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 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 Jesduvroq , or dosing strategy that does not increase these risks. Use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions. 

Clinical Trial Results

The FDA approval of Jesduvroq was based on results from the ASCEND-D trial. The trial enrolled 2,964 dialysis patients with anemia of CKD who were switched to receive daprodustat ESA control from a standard of care ESA therapy. A uniform iron management protocol was instituted across both arms of the study. The study met its primary efficacy and safety endpoints. Results showed daprodustat improved or maintained Hb within target levels (10-11.5 g/dL) for these patients, and the primary safety analysis of the ITT population showed that daprodustat achieved non-inferiority of MACE compared to ESA control.