Daprodustat, an oral medication, has received approval from the U.S. Food and Drug Administration (FDA) for treating anemia associated with chronic kidney disease (CKD) in adults undergoing dialysis. It is the first oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) to be approved in the United States for this specific condition. The availability of an oral treatment option offers a new approach for managing anemia in patients who have been on dialysis for an extended period.
Understanding Daprodustat and Anemia of Chronic Kidney Disease
Daprodustat, marketed as Jesduvroq, functions as an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). This mechanism involves stabilizing hypoxia-inducible factors (HIFs), which are proteins that play a role in the body’s response to low oxygen levels. By inhibiting certain enzymes, daprodustat promotes the production of erythropoietin, a hormone that stimulates the bone marrow to create red blood cells. This action mimics the body’s natural physiological response to high altitude, where increased erythropoietin production helps to correct anemia.
Anemia of chronic kidney disease is a common complication. This condition occurs primarily because damaged kidneys are unable to produce sufficient amounts of erythropoietin, the hormone responsible for signaling the body to make red blood cells. Additionally, reduced iron absorption can contribute to anemia in CKD patients.
The impact of anemia in CKD patients leads to symptoms such as fatigue, weakness, pale skin, dizziness, and difficulty concentrating. Untreated anemia in CKD patients is associated with a greater risk of hospitalization, increased risk of heart problems as the heart works harder to deliver oxygen, and potentially a higher risk of death. Maintaining hemoglobin levels within a specific range is therefore a goal in managing this condition to mitigate these risks.
The FDA’s Review and Approval Process
The FDA’s decision to approve daprodustat for anemia of chronic kidney disease in adults receiving dialysis was based on clinical trial data. Daprodustat’s approval specifically targets adults who have been undergoing dialysis for at least four months.
The approval relied on results from the ASCEND Phase III clinical trial program, which consisted of five trials. These trials, involving over 8,000 patients treated for up to 4.26 years, assessed the efficacy and safety of daprodustat across the spectrum of CKD. Results from the cardiovascular outcomes trial, ASCEND-D, which focused on dialysis patients, were published in the New England Journal of Medicine. These studies demonstrated that daprodustat could improve or maintain hemoglobin levels within a target range of 10-11.5 g/dL without increasing major adverse cardiovascular events (MACE) when compared to standard erythropoiesis-stimulating agents (ESAs).
The CRDAC voted 13-3 that the benefits of daprodustat outweighed its risks for adult dialysis patients with anemia of CKD. However, for adult non-dialysis patients with anemia of CKD, the CRDAC voted 11-5 against the benefit outweighing the risks. This distinction highlights the specific patient population for which daprodustat received approval.
Implications for Patient Care
The approval of daprodustat offers a new oral treatment option for adults with anemia of chronic kidney disease who are receiving dialysis. Currently, other FDA-approved treatments for anemia in CKD are administered as injections, either intravenously or subcutaneously.
This oral formulation may offer increased convenience for patients, potentially simplifying their treatment regimen and reducing the need for frequent injections. While daprodustat has shown non-inferiority to ESAs in maintaining hemoglobin levels and cardiovascular outcomes in dialysis patients, discussions with healthcare providers are important to determine the most appropriate treatment option for individual patients.
Healthcare providers should consider daprodustat as a new option within the existing treatment landscape for anemia of CKD in dialysis patients. Patients and providers should be aware of potential side effects, which include an increased risk of thrombotic vascular events such as blood clots, heart attack, or stroke. Daprodustat is available in five dosage strengths: 1mg, 2mg, 4mg, 6mg, and 8mg tablets, allowing for flexible dosing based on patient needs.