Akebia Therapeutics announces top-line results from PRO2TECT, the second of its two global Phase 3 cardiovascular outcomes programs. The two PRO2TECT studies evaluated the efficacy and safety of vadadustat, Akebia's investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), versus darbepoetin alfa for the treatment of anemia due to chronic kidney disease (CKD) in adult patients not on dialysis. The Company's vadadustat development program also includes two other global Phase 3 studies (INNO2VATE) for the treatment of anemia due to CKD in adult patients on dialysis, for which the Company reported positive top-line data in May.

Vadadustat achieved the primary and key secondary efficacy endpoint in each of the two PRO2TECT studies, demonstrating non-inferiority (NI) to darbepoetin alfa as measured by a mean change in hemoglobin (Hb) between baseline and the primary evaluation period (weeks 24 to 36) and secondary evaluation period (weeks 40 to 52). Vadadustat did not meet the primary safety endpoint of the PRO2TECT program, defined as non-inferiority of vadadustat versus darbepoetin alfa in time to first occurrence of major adverse cardiovascular events (MACE), which is the composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke across both PRO2TECT studies.

Akebia is working to present the full dataset from its global Phase 3 program (INNO2VATE and PRO2TECT) at an upcoming medical conference and publish the data in peer reviewed journals. Akebia plans to submit to the U.S. Food and Drug Administration (FDA) a New Drug Application (NDA) for vadadustat for the treatment of anemia due to CKD in adult dialysis-dependent and non-dialysis dependent patients as early as possible in 2021. Akebia and its collaborator, Otsuka Pharmaceutical Co. Ltd., are working in close collaboration to prepare a Marketing Authorization Application (MAA) for submission to the European Medicines Agency (EMA).

"We remain confident that we have a path toward potential approval for vadadustat in dialysis supported by positive top-line results for efficacy and safety from INNO2VATE. PRO2TECT delivered positive top-line efficacy results; however, the MACE result presents challenges to achieving our goal of bringing vadadustat to patients in the non-dialysis market. While achieving the MACE endpoint would have made our path here more straightforward, as it is in dialysis, we still believe we have a path toward approval for vadadustat in non-dialysis," said John P. Butler, President and Chief Executive Officer of Akebia Therapeutics. "We believe the cardiovascular safety of vadadustat is supported by the totality of the data from our global Phase 3 program, including additional analyses on cardiovascular outcomes observed within key geographic regions and across certain patient sub-populations within PRO2TECT."