FibroGen Announces Analysis of Peritoneal Dialysis Patients With Chronic Kidney Disease From Roxadustat (FG-4592) Incident Dialysis Study

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FibroGen Inc. (FibroGen) today announced the presentation of a Phase 2 subgroup analysis comparing treatment response to roxadustat (FG-4592) a first-in-class oral compound in late stage development in incident peritoneal dialysis (PD) patients and incident hemodialysis (HD) patients for the treatment of anemia in end stage renal disease (ESRD).

This analysis was presented in an oral session at the 2013 American Society of Nephrology (ASN) Kidney Week in Atlanta Georgia.

Roxadustat is an orally administered small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase. HIF is 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 and iron is incorporated into hemoglobin (Hb).

The prevalence of peritoneal dialysis is estimated to represent more than 10% of the global dialysis population and is believed to be growing at a high rate. Noted for its convenience accessibility and lower-cost peritoneal dialysis generally can be self-administered by ESRD patients in the setting of their own home. In the present analysis use of roxadustat to correct anemia in patients (mean hemoglobin baseline =10.0 g/dL) with ESRD who recently started PD is compared to previously reported results of a Phase 2 study of roxadustat to correct anemia in HD patients. Neither patient group had previously been treated with an erythropoiesis-stimulating agent (ESA). Neither patient group received parenteral (intravenous) iron during anemia correction over 12 weeks and both patient groups depended solely on oral iron. A Hb increase of 3.3 g/dL in PD patients (from baseline Hb = 8.8 g/dL) and 3.5 g/dL increase in HD patients (from baseline Hb = 8.5 g/dL) was observed over 12 weeks with 100% of PD and 93% of HD patients achieving a Hb response (Hb increased by =1 g/dL from baseline).

The analysis presented at ASN 2013 showed roxadustat achieved a comparable and significant correction of anemia with average Hb increases of over 3 g/dL when supplemented with only oral iron in both incident PD patients and incident HD patients regardless of dialysis modality. This finding contrasts with reports that intravenous iron supplementation is necessary to achieve optimal erythropoiesis in dialysis patients on current ESA therapy with the Hb response in ESA-treated patients receiving oral iron being no different than that in those receiving no iron supplementation. (Macdougall et al (1996) Kidney Int. 50:1694-1699.) The use of supplemental oral iron with roxadustat appears to be sufficient to achieve robust hemoglobin response in PD patients and in HD patients even in those patients displaying elevated levels of C-reactive protein a measure associated with inflammation and dampened responsiveness to ESA therapy.

Thomas B. Neff Chief Executive Officer of FibroGen noted “This new analysis suggests that roxadustat has the potential to address the medical need of peritoneal dialysis patients as well as hemodialysis patients while avoiding the safety concerns intravenous iron requirements and injections associated with ESA therapy. We remain encouraged by the potential therapeutic advantages of roxadustat including its ability to treat anemia safely and effectively by modest increases in erythropoietin levels to within physiological range while promoting iron bioavailability through multiple synchronized processes.”

About Chronic Kidney Disease (CKD) and Anemia

Diabetes high blood pressure and other conditions can cause significant damage to the kidneys. If left untreated those can result in chronic kidney disease and progress to kidney failure. Such deterioration can lead to patients needing a kidney transplant or being placed on dialysis to remove excess fluid and toxins that build up in the body. The progression of CKD also increases the prevalence of anemia a condition associated with having fewer of the red blood cells that carry oxygen through the body and/or lower levels of hemoglobin the protein that enables red blood cells to carry oxygen. As hemoglobin falls the lower oxygen-carrying capacity of an anemic patients’ blood results in various symptoms including fatigue loss of energy breathlessness and angina. Anemia in CKD patients has been associated with increased hospitalization rates increased mortality and reduced quality of life.

Chronic kidney disease is a worldwide critical healthcare problem that affects millions of people and drives significant healthcare cost. In the US prevalence of CKD has increased dramatically in the past 20 years from 10 percent of the adult population (or approximately 20 million U.S. adults) as stated in the National Health and Nutrition Evaluation Survey (NHANES) 1988-1994 to 15 percent (or approximately 30 million U.S. adults) in NHANES 2003-2006. In 2009 total Medicare costs for CKD patients were $34 billion. China has an estimated 145 million CKD patients or approximately five times the number of CKD patients in the U.S. (Lancet April 2012).

About Roxadustat / FG-4592

Roxadustat (FG-4592) is an orally administered small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase activity in development for the treatment of anemia in patients with chronic kidney disease (CKD). HIF is a protein transcription factor that induces the natural physiological response to conditions of low oxygen “turning on” erythropoiesis (the process by which red blood cells are produced) and other protective pathways. Roxadustat has been shown to correct anemia and maintain hemoglobin levels without the need for supplementation with intravenous iron in CKD patients not yet receiving dialysis and in end-stage renal disease patients receiving dialysis. An Independent Data Monitoring Committee has found no signals or trends to date to suggest that treatment with roxadustat is associated with increased risk of cardiovascular events thrombosis or increases in blood pressure requiring initiation or intensification of antihypertensive medications.

About FibroGen

FibroGen is a privately-held biotechnology company focused on the discovery development and commercialization of therapeutic agents for treatment of fibrosis anemia cancer and other serious unmet medical needs. FibroGen’s FG-3019 monoclonal antibody is in clinical development for treatment of idiopathic pulmonary fibrosis and other proliferative diseases including pancreatic cancer and liver fibrosis. Roxadustat (FG-4592) FibroGen’s small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase is currently in clinical development for the treatment of anemia. FibroGen is also currently pursuing the use of proprietary recombinant human type III collagens in synthetic corneas for treatment of corneal blindness.