The FDA has approved daprodustat, the first oral treatment for anemia for adults receiving dialysis for at least 4 months. Daprodustat is the first hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) to obtain FDA approval.
“With an oral drug option in addition to the FDA-approved injection options, adults with chronic kidney disease on dialysis now have multiple ways to treat their anemia,” Ann Farrell, MD, director of the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research, stated in a news release. Daprodustat inhibits oxygen-sensing prolyl hydroxylase enzymes and stabilizes hypoxia-inducible factors, which leads to transcription of erythropoietin and an increase in hemoglobin levels. Oral daprodustat, marketed as Jesduvroq by GlaxoSmithKline, is available in 5 dosage strengths: 1 mg, 2 mg, 4 mg, 6 mg, and 8 mg.
Conventional anemia treatment for the dialysis population involves infusion of erythropoiesis-stimulating agents (ESAs). The FDA approval of daprodustat is based on results from the ASCEND-D trial comparing daprodustat with ESAs, published in the New England Journal of Medicine, and follows a favorable FDA committee vote in October 2022.
A GlaxoSmithKline news release cautioned that targeting a hemoglobin level greater than 11 g/dL in patients with anemia may further increase the risk of death and arterial venous thrombotic events, as occurs with ESAs. “No trial has identified a hemoglobin target level, daprodustat dose, or dosing strategy that does not increase these risks,” it read. “Use the lowest dose of Jesduvroq sufficient to reduce the need for red blood cell transfusions.”
The most common side effects of daprodustat include high blood pressure, thrombotic vascular events, abdominal pain, dizziness, and allergic reactions.
Daprodustat carries a boxed warning for an increased risk of thrombotic vascular events including death, heart attack, stroke, and blood clots in the lungs, legs, or dialysis access site. Additional warnings and precautions include a risk of hospitalization for heart failure, worsening increase of blood pressure, and stomach erosions and gastrointestinal bleeding.
Daprodustat is not approved for patients with nondialysis-dependent chronic kidney disease because its safety has not been established in this population.
Disclosure: The ASCEND-D trial was supported by GlaxoSmithKline. Please see the original references for a full list of disclosures.
FDA approves first oral treatment for anemia caused by chronic kidney disease for adults on dialysis. News release. FDA; February 1, 2023.
Jesduvroq (daprodustat) approved by US FDA for anaemia of chronic kidney disease in adults on dialysis. News release. GlaxoSmithKline; February 1, 2023.