Akebia Therapeutics Announces Positive Top-Line Results from Global Phase 3 Program of Vadadustat for Treatment of Anemia Due to Chronic Kidney Disease in Adult Patients on Dialysis

The INNO2VATE Correction/Conversion study evaluated 369 incident dialysis patients (181 and 188 patients randomized to vadadustat and darbepoetin alfa, respectively) who initiated chronic dialysis (either peritoneal dialysis (PD) or hemodialysis (HD)) for end-stage renal disease (ESRD) ≤ 16 weeks prior to screening and had limited exposure to recombinant erythropoiesis stimulating agents (rESAs). The INNO2VATE Conversion study evaluated 3,554 dialysis patients (1,777 and 1,777 patients randomized to vadadustat and darbepoetin alfa, respectively) currently receiving rESA who were converted to either vadadustat or darbepoetin alfa.

In both INNO2VATE studies, the primary efficacy endpoint was the mean change in Hb between baseline and the primary evaluation period (weeks 24-36). NI was achieved if the lower bound of the 95% confidence interval for the between-group difference of the mean Hb change did not fall below the pre-specified NI margin (-0.75 g/dL). The INNO2VATE program’s primary safety endpoint, MACE, was independently and blindly assessed by the Brigham and Women’s Hospital’s Clinical Endpoint Center (BWH CEC) in Boston, MA, with a comparison of vadadustat to darbepoetin alfa. MACE is defined as the composite endpoint of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke. To assess MACE, a combined analysis of time to first MACE event from the two INNO2VATE studies was performed. NI was achieved if the upper bound of the 95% confidence interval for the hazard ratio of vadadustat to darbepoetin alfa did not exceed the pre-specified NI margin of 1.25.

Primary and Key Secondary Efficacy Endpoint Results
Vadadustat achieved each of the INNO2VATE studies’ primary efficacy endpoints of mean change in Hb between baseline and the primary evaluation period (mean Hb from weeks 24 to 36) compared to darbepoetin alfa, in adult patients on dialysis, demonstrating non-inferiority to darbepoetin alfa based on using a non-inferiority margin of -0.75 g/dL prospectively agreed to with FDA and EMA.

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