Akebia Therapeutics announced positive top-line results from INNO2VATE, the global phase-III cardiovascular outcomes program evaluating the efficacy and safety of vadadustat versus darbepoetin alfa for the treatment of anemia due to Chronic Kidney Disease (CKD) in adult dialysis-dependent patients (DD-CKD). Vadadustat achieved the primary and key secondary efficacy endpoints in each of the two INNO2VATE studies, demonstrating non-inferiority to darbepoetin alfa.
Akebia’s global INNO2VATE program includes two separate Phase 3 studies (Correction/Conversion and Conversion), which collectively enrolled 3,923 adult patients on dialysis with anemia due to CKD. Both INNO2VATE studies are global, multicenter, open label (sponsor blinded), active-controlled (darbepoetin alfa – an injectable erythropoiesis stimulating agent (ESA)), non-inferiority studies. In both studies, patients were randomized 1:1 to receive either vadadustat or darbepoetin alfa. Vadadustat was initiated at a starting oral dose of 300 mg once daily and adjusted over time in increments of 150 mg within the range of 150 to 600 mg daily, while darbepoetin alfa was dosed per the drug label guidelines.
Patients treated with vadadustat achieved the primary and key secondary efficacy endpoint in each of the two INNO2VATE studies, demonstrating non-inferiority 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 also achieved the primary safety endpoint of the INNO2VATE program, defined as non-inferiority of vadadustat versus darbepoetin alfa in time to first occurrence of major adverse cardiovascular events (MACE), which is a composite of all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke across both INNO2VATE studies. Each analysis was measured against non-inferiority (NI) margins agreed upon with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
The Phase 3 program includes the PRO2TECT studies of vadadustat for the treatment of anemia due to CKD in adult patients not on dialysis. The Company expects read out data in mid-2020. Following completion of the program, Akebia plans to submit to FDA an NDA for vadadustat for the treatment of anemia due to CKD in adult dialysis-dependent and non-dialysis dependent patients. Collaboration partner Otsuka Pharmaceutical Co. also plans to submit a Marketing Authorization Application (MAA) to EMA. A Japanese New Drug Application (JNDA) for vadadustat was submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) in July 2019 by Mitsubishi Tanabe Pharma Corporation (MTPC), Akebia’s development and commercialization collaboration partner in Japan for vadadustat.
Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower oxygen availability with stabilization of hypoxia-inducible factor, which can lead to increased red blood cell production and improved oxygen delivery to tissues.
About Anemia due to Chronic Kidney Disease (CKD)
Anemia is a condition in which a person lacks enough healthy red blood cells to carry adequate oxygen to the body’s tissues. It commonly occurs in people with CKD because their kidneys do not produce enough erythropoietin (EPO), a hormone that helps regulate production of red blood cells. Anemia due to CKD can have a profound impact on a person’s quality of life as it can cause fatigue, dizziness, shortness of breath and cognitive dysfunction. Left untreated, anemia leads to deterioration in health and is associated with increased morbidity and mortality in people with CKD.