Akebia starts phase 3 PRO2TECT program

This program is evaluating vadadustat (formerly AKB-6548) in non-dialysis patients with anemia related to chronic kidney disease (NDD-CKD).

In addition, the U.S. Food and Drug Administration (FDA) recently opened Akebia’s Investigational New Drug (IND) application, allowing the company to initiate a Phase 1 clinical study of AKB-6899, an orally-available HIF stabilizer, in oncology. The company also made progress with its intellectual property efforts in Japan for vadadustat.

Akebia president and CEO John Butler said: "We achieved all of our clinical and corporate objectives for 2015, positioning Akebia for continued success with the vadadustat anemia program in chronic kidney disease and further building our pipeline of HIF stabilizers.

"The launch of our global Phase 3 PRO2TECT program in non-dialysis patients is a significant milestone in our efforts to establish vadadustat as the best-in-class treatment option for chronic kidney disease patients with anemia. Following positive Phase 2 data for vadadustat in dialysis patients, we are now working with regulators to finalize the design for our INNO2VATE global Phase 3 program, which is expected to commence this year."

Mr. Butler added, "We were also very pleased to have announced a collaboration with Mitsubishi Tanabe, one of the largest and most successful pharmaceutical companies in Japan, for the development and commercialization of vadadustat in Japan and certain other Asian countries. Additionally, the FDA opened an IND for our second HIF stabilizing compound, AKB-6899, and we expect to initiate a Phase 1 study in oncology this year. We look forward to continuing to build on this momentum in 2016 and beyond."

PRO2TECT Program Update

The PRO2TECT Phase 3 program includes two separate studies that will collectively enroll approximately 3,100 NDD-CKD patients across 500 sites globally. The first patient was recently dosed in the PRO2TECT™ correction study, which is enrolling anemic patients not currently being treated with recombinant erythropoiesis stimulating agents (rESAs).

The PRO2TECT conversion study includes patients currently receiving rESA who will be converted to either vadadustat or the active control with the goal of maintaining their baseline hemoglobin levels. Both studies include a 1:1 randomization and an open label, active-control, non-inferiority design. Primary endpoints include an efficacy assessment of the hemoglobin response and cardiovascular safety as measured by major adverse cardiovascular events.

The PRO2TECT program is designed to support registration in major markets worldwide and to collect the data required to establish a new standard of care for chronic kidney disease (CKD) patients. The company expects to complete enrollment in late 2017.

"The PRO2TECT™ Phase 3 program builds on our robust Phase 2 program in NDD-CKD patients, which found that once-daily vadadustat maintained hemoglobin levels in a clinically relevant range while minimizing fluctuations in hemoglobin levels that are associated with increased cardiovascular safety risks," stated Brad Maroni, M.D., Chief Medical Officer at Akebia. "These studies are designed to establish the safety and efficacy of vadadustat in the setting of contemporary clinical practice, and to support regulatory approvals globally."

AKB-6899 Update

The company’s second clinical candidate, AKB-6899, is designed as a small molecule HIF stabilizer with potential therapeutic benefit in oncology and ophthalmology. In in vitro studies, AKB-6899 reduced VEGF levels in the presence of hypoxia, and therefore has the potential to reduce VEGF in tumor cells specifically.

In several preclinical models, AKB-6899 reduced tumor growth and the development of metastases. Therefore, Akebia opened an IND with the FDA at the end of 2015 and expect to commence clinical development of AKB-6899 in 2016.

Intellectual Property Update

Akebia is pleased to provide an update on its challenge to Japanese Patent No. 4804131 (the ‘131 patent), which is owned by FibroGen. On June 2, 2014, Akebia filed an invalidity proceeding in the Japanese Patent Office (JPO) challenging the validity of the ‘131 patent, requesting that it be revoked in its entirety. In a preliminary decision dated May 11, 2015, the JPO found all of the challenged claims to be invalid. In response, FibroGen filed a request for correction in which it requested that the ‘131 patent claims be amended to exclude pyridine carboxamides from their scope.

On November 18, 2015, Akebia received the final trial decision from the JPO in which it accepted FibroGen’s requested claim amendments. As a result of the JPO’s decision and FibroGen’s subsequent amendments, the FibroGen ‘131 patent does not cover vadadustat or any pyridine carboxamide compounds.

About Vadadustat

Vadadustat is an oral therapy currently in development for the treatment of anemia related to CKD. Vadadustat is designed to stabilize HIF, a transcription factor that regulates the expression of genes involved with red blood cell (RBC) production in response to changes in oxygen levels, by inhibiting the HIF prolyl-hydroxylase enzyme. Vadadustat exploits the same mechanism of action used by the body to naturally adapt to lower oxygen availability associated with a moderate increase in altitude.

The body responds to lower oxygen availability with increased production of HIF, which coordinates the interdependent processes of iron mobilization and erythropoietin (EPO) production to increase RBC production and, ultimately, improve oxygen delivery.

As a HIF stabilizer with best-in-class potential, vadadustat raises hemoglobin levels predictably and sustainably, with a dosing regimen that allows for a gradual and controlled titration. Vadadustat has been shown to improve iron mobilization, potentially reducing the need for iron supplementation.

About Anemia Related to CKD

Approximately 30 million people in the United States have CKD, with an estimated 1.8 million of these patients suffering from anemia. Anemia results from the body’s inability to coordinate RBC production in response to lower oxygen levels due to the progressive loss of kidney function, which occurs in patients with CKD.

Left untreated, anemia significantly accelerates patients’ overall deterioration of health with increased morbidity and mortality. Renal anemia is currently treated with injectable rESAs, which are associated with inconsistent hemoglobin responses and well-documented safety risks.