FibroGen Reports Data from Phase 2 Study of FG-4592 Hemoglobin Correction and Maintenance in End-Stage Renal Patients
FibroGen, Inc., today announced that data from an ongoing Phase 2 study of FG-4592, an orally delivered, small molecule treatment for anemia, were presented on 2 November 2012, at the American Society of Nephrology (ASN) Kidney Week 2012 in San Diego, California. The study was designed to compare FG-4592 , an investigational hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), with an active comparator (epoetin α) in patients with end-stage renal disease (ESRD) receiving hemodialysis, whose hemoglobin (Hb) levels were previously maintained with intravenous (IV) epoetin α and IV iron supplementation.
FG-4592 is a novel small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase. This randomized Phase 2 study of the efficacy and safety of FG-4592 in maintaining and correcting hemoglobin (Hb) is the first proof-of-concept and dose-finding clinical study evaluating the use of FG-4592, a HIF prolyl hydroxylase inhibitor, in treating anemia in ESRD patients undergoing chronic hemodialysis, whose Hb levels were previously maintained with epoetin α, an erythropoiesis-stimulating agent (ESA). The study (Study 040) included a number of treatment cohorts with different starting doses, each consisting of 16 patients randomized to FG-4592 or to epoetin α. This exploratory study was intended to evaluate a wide range of hemodialysis patients, including those receiving high and low doses of epoetin α at baseline. 146 patients were randomized, and 143 received either FG-4592 or epoetin α. IV iron supplementation was not allowed in this study.
Results presented at American Society of Nephrology (ASN) Kidney Week 2012, in San Diego, California, show that FG-4592 was able to correct and maintain hemoglobin levels for 19 weeks without IV iron supplementation in patients previously receiving maintenance epoetin α. In addition, levels of hepcidin, the key regulator of iron homeostasis, were significantly lower in FG-4592-treated patients than in the active control patients; elevated levels of hepcidin have been shown to decrease iron absorption. Further, a marked and sustained reduction in total plasma cholesterol levels by an average of 20% was observed in FG-4592-treated patients, while no reduction was seen in patients treated with epoetin α (active comparator). As dyslipidemia is highly prevalent in chronic kidney disease patients, and a major cardiovascular risk factor in this population, management of dyslipidemia is an important component of therapeutic strategy for CKD patients. Data suggesting that treatment of FG-4592 could improve a patient's lipid profile, and eliminate or minimize the need for concomitant medications, points to another potential advantage over current ESA-based therapies.
“There is a need for alternative anemia therapies,” said Thomas B. Neff, Chief Executive Officer of FibroGen, Inc. “Side effects associated with current treatments include exposure to supraphysiologic erythropoietin levels, and depletion of iron stores. Preliminary clinical findings show that FG-4592 was able to correct and maintain hemoglobin levels in ESRD patients, and to do so with peak erythropoietin levels within physiologic range. Further, patients treated with FG-4592 showed no functional iron deficiency, even without the administration of intravenous iron. These results suggest FG-4592 could be a safe and effective alternative to ESAs in the treatment of anemia CKD patients.”
The efficacy and safety of FG-4592 will be further investigated in pivotal Phase 3 clinical trials.
About Anemia of Chronic Kidney Disease (CKD)
CKD is a worldwide critical healthcare problem that affects millions of people and drives significant healthcare cost. In the U.S., prevalence of CKD has increased dramatically in the past 20 years, from 10% of the U.S. adult population (or approximately 20 million U.S. adults) per the National Health and Nutrition Evaluation Survey (NHANES) 1988-1994, to 15% (or approximately 30 million adults) in NHANES 2003-2006. In 2009, total Medicare costs for CKD patients were $34 billion.
Anemia is the condition of having fewer red blood cells and/or lower hemoglobin levels than is normal. The prevalence of anemia increases with the progression of CKD and is a demonstrated risk multiplier in patients with preexisting cardiovascular disease. Anemia has been associated with adverse outcomes in CKD patients, increased hospitalization rates, increased mortality, and reduced quality of life, but the condition tends to be undertreated due in part to the cost and complexity of treatment with injectable erythropoiesis-stimulating agents (ESAs) and intravenous iron supplements. Whereas nearly all patients on hemodialysis have easy access to ESA therapy, only 2% of CKD patients receive treatment with ESAs prior to referral to a nephrologist in the U.S.1 Under-treatment of anemia in the primary care setting can be attributed in part to lack of convenience and reimbursement rules, requiring physicians to buy ESA inventory and bill after procedures. This deters physicians in the primary care setting where anemic patients are a minority of total patients. The company estimates there are 1 million late-stage CKD patients (CKD Stages 3-5) with anemia in the U.S., and less than 20% are treated with ESAs prior to initiation of dialysis.1
FibroGen is developing FG-4592, a novel oral HIF-PHI, for the treatment of anemia in patients with CKD. FG-4592 has been shown to correct and maintain hemoglobin levels in patients with CKD not receiving dialysis2 and in patients with end-stage renal disease receiving dialysis3 without the need for supplementation with intravenous iron. An Independent Data Monitoring Committee has found no signals or trends to date to suggest that treatment with FG-4592 is associated with increased risk of cardiovascular events, thrombosis, or increases in blood pressure requiring initiation or intensification of antihypertensive medications.
Global Development of FG-4592
FG-4592 is in clinical development in the U.S., Europe, Japan, and the People's Republic of China. Multiple clinical trials in the U.S. have progressed toward commencement of Phase 3 clinical development in the U.S. and Europe by the end of 2012. In Japan, Astellas has completed Phase 1 studies and plans to begin Phase 2 studies soon. On September 20, 2010, FibroGen announced that the Chinese State Food and Drug Administration had granted FibroGen a clinical trial application approval to commence Phase 1 and Phase 2 clinical development for FG-4592 for the treatment of anemia associated with CKD in the People's Republic of China. Phase 1 in China is completed, and FibroGen has completed dosing in all patients in two Phase 2 studies in CKD anemia, in patients on dialysis and in patients not on dialysis. Phase 3 clinical development in China is expected to commence in 2013.
Astellas has licensed certain rights from FibroGen to FG-4592 (Astellas designation ASP1517) in Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa. As part of these agreements, Astellas pays 50% of development costs for FG-4592 in the U.S. and Europe, and makes milestone payments for clinical advancement and approvals in Europe and in Japan, as well as other subsequent events. FibroGen retains rights to its anemia therapies in North America and South America, remaining parts of Africa, and all of Asia Pacific ex-Japan.
About FibroGen, Inc.
FibroGen, Inc., is a biotechnology company focused on the discovery, development, and commercialization of therapeutics for fibrosis, anemia, cancer, and other serious unmet medical needs. FibroGen's research into the role of CTGF in various proliferative diseases has led to the development of therapies for the treatment of idiopathic pulmonary fibrosis and cancers, including pancreatic cancer, and other life-threatening disorders. FibroGen's expertise in the area of prolyl hydroxylase inhibition has led the development of an extensive library of small molecule inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, including FG-4592 and FG-6874, currently in clinical development for the treatment of anemia. FibroGen also develops and produces recombinant biomaterials, such as human collagens and gelatins, for various purposes, and is currently pursuing the use of recombinant human type III collagen in synthetic corneas for treatment of corneal blindness. FibroGen was founded in 1993 and is based in San Francisco, California.
For more information about FibroGen, Inc., please visit www.fibrogen.com.
1. U.S. Renal Data System, USRDS 2012 Annual Data Report: Atlas of Chronic Kidney and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2012
2. Besarab A, et al (2011) J Am Soc Nephrol 22:196A
3. Provenzano R, et al. (2011) Am. J. Kidney Dis Vol. 57 4:B80
Meichiel Keenan, 415-978-1431