Akebia Therapeutics  is initiating  a global Phase 3 clinical trial program, called INNO₂VATE, to evaluate vadadustat for chronic kidney disease-related anemia.

The company’s lead candidate, vadadustat, is an oral therapy being developed for the treatment of anemia linked to chronic kidney disease (CDK) in both dialysis and non-dialysis patients.

Anemia occurs due to the inability to coordinate red blood cell production in response to lower oxygen levels. In CKD patients, anemia is caused by the progressive loss of kidney function and, if left untreated, can significantly accelerate disease progression. Renal anemia is currently treated with injectable recombinant erythropoiesis stimulating agents (rESAs), but these drugs have been linked to inconsistent hemoglobin responses and well-documented safety risks.

Vadadustat is an oral hypoxia-inducible factor (HIF) stabilizer with best-in-class potential for the treatment of CKD-related anemia. Currently in development, vadadustat uses a smiliar mechanism of action to that our bodies use naturally to adapt to lower oxygen availability associated with a moderate increase in altitude. At higher altitudes, the body responds to lower oxygen levels with increased HIF production, which coordinates the interdependent processes of iron mobilization and erythropoietin production to boost the number of red blood cells, thereby improving oxygen delivery.

INNO₂VATE consists of two studies designed to evaluate vadadustat in patients with anemia related to chronic kidney disease who are undergoing dialysis. Akebia’s ongoing Phase 3 PRO₂TECT program (NCT02648347) in non-dialysis dependent patients with anemia related to chronic kidney disease began late last year and is expected to conclude in 2018.

INNO₂VATE includes two separate studies (INNO₂VATE-Correction and INNO₂VATE-Conversion) and will enroll a total of 2,600 dialysis-dependent participants with anemia related to CKD. Both are designed as open-label and active-control, and will be randomized at a 1:1 ratio. Primary endpoints will include an efficacy assessment of the hemoglobin response and an assessment of cardiovascular safety as measured by standard major adverse cardiovascular events (MACE) criteria.

INNO₂VATE-Correction will assess patients who are not currently receiving treatment with rESAs. INNO₂VATE-Conversion will evaluate patients currently under rESA treatment, who will be converted to either vadadustat or the study’s active control in order to maintain their baseline hemoglobin levels.

“The launch of the INNO₂VATE program represents an important milestone for our global vadadustat Phase 3 program,” John P. Butler, Akebia’s president and chief executive officer, said in a press release. “Similar to our parallel Phase 3 PRO₂TECT program in patients who are not currently on dialysis, INNO₂VATE is designed to demonstrate the best-in-class potential of vadadustat to treat patients who are suffering from anemia related to chronic kidney disease.”