AstraZeneca and biotechnology company FibroGen have entered into a collaboration to develop and commercialize FG-4592, a first-in-class oral compound in late stage development for the treatment of anemia associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), which also may be extended to other anemia indications.

This collaboration focuses on the U.S., China and all major markets excluding Japan, Europe, the Commonwealth of Independent States, the Middle East and South Africa, which are covered by an existing agreement between FibroGen and Astellas Pharma.

FG-4592 is a small molecule inhibitor of hypoxia-inducible factor (HIF), a protein that responds to oxygen changes in the cellular environment and meets the body’s demands for oxygen by inducing erythropoiesis, the process by which red blood cells are produced. FG-4592 has the potential to address the unmet medical need for an effective treatment for anemia that offers the convenience of oral administration and an improved safety profile as compared to current standards of care. Current treatment options involve a combination of injectable erythropoiesis-stimulating agents (ESAs) and iron supplements. FG-4592 works through the body’s natural oxygen-sensing and response system to help produce red blood cells. This can be compared to the body’s natural response to conditions at high altitude, where oxygen levels are low, which is to produce more red blood cells.

In phase II clinical studies, FG 4592 met its primary objective of demonstrating anemia correction in treatment-naïve CKD patients not on dialysis as well as maintenance of hemoglobin levels and anemia correction in patients on dialysis. FG 4592 has demonstrated this efficacy combined with an acceptable safety profile in clinical trials, and has been shown to achieve anemia correction in the absence of intravenous iron supplementation.

The companies plan to undertake an extensive FG-4592 phase III development program for the U.S., and to initiate phase III trials in China, with anticipated regulatory filings in China in 2015 and in the U.S. in 2017.

AstraZeneca will pay FibroGen committed upfront and subsequent non-contingent payments totaling $350 million, as well as potential future development related milestone payments of up to $465 million, and potential future sales related milestone payments in addition to tiered royalty payments on future sales on FG-4592 in the low 20% range.

AstraZeneca will be responsible for the U.S. commercialization of FG-4592, with FibroGen undertaking specified promotional activities in the ESRD segment in this market. The companies will also co-commercialize FG-4592 in China where FibroGen will be responsible for clinical trials, regulatory matters, manufacturing and medical affairs, and AstraZeneca will oversee promotional activities and commercial distribution.

“We know from our research into complications of renal disease that anemia continues to be a challenge for patients with chronic kidney disease, due in part to the inconvenience and complexity of existing injectable and intravenous therapies and the safety concerns associated with them,” said Pascal Soriot, chief executive officer, AstraZeneca.

 “FG-4592 has the potential to offer anaemia patients an oral therapy that provides coordinated erythropoiesis, that increases natural erythropoietin within the normal physiological range, and that is effective without intravenous iron supplementation and without an increased risk for hypertension,” said Thomas B. Neff, chief executive officer, FibroGen.