Vafseo Approved for Anemia Due to CKD in Patients on Dialysis – Renal and Urology News

The Food and Drug Administration (FDA) has approved Vafseo^® (vadadustat) for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least 3 months.

Vafseo is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that increases the production of erythropoietin. The approval was based on data from the randomized, active-controlled, noninferiority, open-label phase 3 INNO₂VATE-1 (ClinicalTrials.gov Identifier: NCT02865850) and INNO₂VATE-2 (ClinicalTrials.gov Identifier: NCT02892149) studies. Both trials evaluated the efficacy and safety of vadadustat for the treatment of anemia in adults with CKD on dialysis. 

Study participants were randomly assigned 1:1 to receive oral vadadustat with a starting dose of 300mg once daily (titrated up to 600mg) or darbepoetin alfa, administered subcutaneously or intravenously, for 52 weeks.

INNO₂VATE-1 included patients with incident dialysis-dependent CKD (DD-CKD) who initiated dialysis within 16 weeks prior to starting the trial and who were erythropoietin stimulating agent (ESA)-naive, had limited prior ESA use or were maintained on ESAs. INNO₂VATE-2 included patients on chronic maintenance dialysis for more than 12 weeks who had converted from prior ESA therapy.

The coprimary endpoints were the mean change in hemoglobin (Hb) from baseline to the primary evaluation period (weeks 24 to 36) and major adverse cardiovascular events (MACE) after 52 weeks, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke. An additional efficacy endpoint was the difference in mean change of Hb from baseline to the secondary evaluation period (weeks 40 to 52).

Results from the both studies showed treatment with vadadustat was noninferior to darbepoetin alfa in correcting and maintaining Hb levels in adults with DD-CKD (pre-specified noninferiority margin of -0.75g/dL):

• INNO₂VATE-1
  • Treatment difference (weeks 24 to 36): -0.3g/dL (95% CI, -0.5, -0.10); 
  • Treatment difference (weeks 40 to 52): -0.1g/dL (95% CI, -0.3, 0.2).
• INNO₂VATE-2
  • Treatment difference (weeks 24 to 36):  -0.2g/dL (95% CI, -0.2, -0.1);
  • Treatment difference (weeks 40 to 52): -0.2g/dL (95% CI, -0.3, -0.1). 

Combined analysis from both studies showed vadadustat was noninferior to darbepoetin alfa in time to first occurrence of MACE (hazard ratio, 0.96; 95% CI, 0.83-1.11), meeting the prespecified noninferiority criterion of 1.25. These results were consistent for the individual components of the MACE endpoint.

The most common adverse reactions reported with Vafseo were hypertension and diarrhea. The prescribing information also includes a Boxed Warning regarding an increased risk for thrombotic vascular events, including MACE. Similar to ESAs, targeting a Hb level greater than 11g/dL is expected to further increase the risk of death and arterial and venous thrombotic events.

Vafseo is supplied in 3 tablet strengths: 150mg, 300mg, and 450mg. It is recommended that the lowest dose sufficient to reduce the need for red blood cell transfusions be used.

This article originally appeared on MPR