Potential best in class
We believe vadadustat (also known as AKB-6548) has compelling clinical data demonstrating a best-in-class profile with several potential safety and efficacy advantages over current injectable erythropoietin stimulating agent (rESA) therapy in the treatment of anemia associated with chronic kidney disease (CKD).
Vadadustat has the potential to significantly increase hemoglobin in anemic CKD patients
In the phase 2a trial vadadustat significantly increased hemoglobin levels compared to baseline in a dose-dependent manner across all treatment arms (P < .0001). Further, vadadustat provides a physiologic reticulocyte response, ie, newly formed red blood cells (RBCs), which leads to a more gradual and consistent increase in hemoglobin levels than what is seen with injectable rESA therapies. This means that these improvements occur without causing patients’ hemoglobin to rise to levels that cause concern.
Vadadustat has the potential to restore the normal diurnal variation of erythropoietin (EPO) for a patient with anemia in a way that an injectable rESA cannot
Instead of binding directly to and saturating the EPO receptor for prolonged periods of time as is the case with current injectable rESA treatments, vadadustat acts by simulating the body’s natural response to hypoxia that is carried out by stabilization of HIFα.
Once-daily, oral dosing
Once-daily, oral dosing of vadadustat offers improved convenience for patients as compared to injectable rESAs. This convenience may increase access to anemia therapy for the largely underserved population of patients with anemia secondary to CKD who are not yet on dialysis and for patients with other forms of anemia, such as idiopathic anemia of aging. Vadadustat offers the potential of flexible oral dosing that provides a more gradual and reliable means of titration than injectable rESAs.
Ability to stabilize the iron supply to the bone marrow while improving hemoglobin production
In clinical trials, vadadustat has demonstrated a dose-related increase in total iron binding capacity. These results indicate that vadadustat has the potential to stabilize the iron supply to the bone marrow while improving hemoglobin production and EPO responsiveness. As a result, unlike injectable rESAs, which have no effect on iron mobilization, vadadustat offers the added potential benefit of reducing the amount of supplemental iron required by anemia patients, often administered intravenously.
Differentiated safety profile
Vadadustat’s novel mechanism of action and dosing profile offer the opportunity to potentially avoid the black box label ascribed to injectable rESAs. In our recently completed phase 2a study, no drug-related serious adverse events were reported. Dosing was well tolerated and there was no evidence of undesirable vascular response.
Vadadustat is an investigational study drug and has not been approved for use by the U.S. Food and Drug Administration (FDA) or any regulatory authority.