Positive topline data were announced from the global phase 3 INNO2VATE program of vadadustat (Akebia Therapeutics) for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis.

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor designed to mimic the physiologic effect of altitude on oxygen availability resulting in increased red blood cell production and improved oxygen delivery to tissues. 

The INNO2VATE program includes the multicenter, randomized, open-label, active-controlled phase 3 Correction/Conversion (N=369) and Conversion (N=3554) studies that compared the efficacy and safety of vadadustat to darbepoetin alfa in adult patients on dialysis with anemia due to CKD. In both studies, patients were randomized to receive an initial dose of vadadustat 300mg orally once daily or darbepoetin alfa. The co-primary end points for both studies were the mean change in hemoglobin (Hb) from baseline to week 36 and major adverse cardiovascular events (MACE), defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke. A key secondary end point was the sustained efficacy response of vadadustat with Hb values within target range during the secondary evaluation period (weeks 40 to 52).

Findings from both studies showed that vadadustat met the primary and key secondary end points achieving noninferiority compared with darbepoetin alfa. In the INNO2VATE Correction/Conversion study, the least square mean difference in Hb was -0.31g/dL (95% CI: -0.53, -0.10) at week 36, meeting the prespecified noninferiority criterion of -0.75g/dL. At weeks 24 to 36, vadadustat-treated patients demonstrated a mean Hb level of 10.36g/dL vs 10.61g/dL for darbepoetin alfa-treated patients. Additionally, vadadustat maintained the target Hb efficacy response at weeks 40 to 52 with a least square mean difference in Hb of -0.07g/dL (95% CI: -0.34, 0.19).

In the INNO2VATE Conversion study, the least square mean difference in Hb was -0.17g/dL (95% CI: -0.23, -0.10) at week 36, meeting the prespecified noninferiority criterion of -0.75g/dL. At weeks 24 to 36, vadadustat-treated patients demonstrated a mean Hb level of 10.36g/dL vs 10.53g/dL for darbepoetin alfa-treated patients. Moreover, vadadustat maintained the target Hb efficacy response at weeks 40 to 52 with a least square mean difference in Hb of -0.18g/dL (95% CI: -0.25, -0.12). 

With regard to safety, both studies met the primary safety end point of noninferiority for MACE. Both studies also demonstrated a similar incidence of adverse events between patients treated with vadadustat and darbepoetin alfa. The incidence of serious treatment-emergent adverse events were slightly lower for patients treated with vadadustat compared with darbepoetin alfa.

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“We look forward to sharing these compelling data with regulators, as well as with physicians, dialysis providers and payers,” said John P. Butler, President and Chief Executive Officer of Akebia Therapeutics. “The team is already at work on vadadustat’s New Drug Application (NDA), which we expect to file as quickly as possible following the top-line data readout of PRO2TECT, our global phase 3 program studying vadadustat in adult patients not on dialysis with anemia due to CKD, which we expect in mid-2020, as planned.”

For more information visit akebia.com.