SAN FRANCISCO, Feb. 16, 2016 (GLOBE NEWSWIRE) -- FibroGen, Inc. (Nasdaq:FGEN) (“FibroGen”), a research-based biopharmaceutical company, today announced that the American Journal of Kidney Disease has published Phase 2 data showing roxadustat, an investigational oral agent for the treatment of anemia in patients with chronic kidney disease (CKD), maintained hemoglobin levels among patients on hemodialysis previously treated with and switched from epoetin alfa - regardless of baseline iron repletion status, degree of inflammation (measured by C-reactive protein (CRP) level), or prior iron regimen - over two time periods of six and 19 weeks. The manuscript is entitled, “Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.”
In the first part of the study, lasting six weeks, roxadustat dosed at its lowest levels (1.0 mg/kg per dose thrice weekly, TIW) maintained hemoglobin at a level comparable to epoetin alfa (defined as hemoglobin remaining stable or not varying from baseline by more than -0.5 mg/dL) (44% v. 33%). Roxadustat doses of 1.5 mg/kg or greater achieved greater Hb response than epoetin alfa, with a pooled response at 6 weeks of 79% compared to 33% in those receiving epoetin alfa.
In the second part of the study, the mean difference between hemoglobin values in subjects receiving roxadustat and epoetin alfa was -0.03 g/dL (95% confidence interval -0.39 to 0.33 g/dL). Examining the primary endpoint, 51% of subjects receiving roxadustat were able to achieve a Hb level > 11.0 g/dL over the last four weeks of the 19-week treatment period compared with 36% of those receiving epoetin alfa. Roxadustat maintenance dose requirements during the last 7 weeks of therapy were not correlated with levels of the inflammatory parameter CRP, even in subjects with average CRP levels elevated above upper limit of normal [(ULN=5 mg/L): n=26/49 (53.1%), median 19.3 mg/L, range 5.5-71.7 mg/L (up to 14x ULN)] during the last 7 weeks of treatment. Further, hemoglobin was maintained within physiologic levels of endogenously produced erythropoietin in the roxadustat-treated subjects tested while reticulocytes were produced and continued to demonstrate stable and adequate hemoglobin concentration in the absence of intravenous iron in these subjects. Finally, consistent with other reported data from the Phase 2 program, decreases in cholesterol and hepcidin were observed during roxadustat treatment.
“This trial showed that conversion to roxadustat from epoetin alfa to treat end-stage renal disease patients on dialysis can be successfully accomplished. The potential ability of roxadustat to treat inflamed patients, a vulnerable population, removing the need for exposure to high erythropoietin levels, is particularly fascinating,” said Robert Provenzano, MD, lead author and chief of the Division of Nephrology, Hypertension & Transplantation, director of Nephrology Research, and director of Acute Dialysis Services at St. John Hospital and Medical Center in Detroit, Michigan. “The potential ability of roxadustat to maintain anemia correction without ongoing intravenous iron repletion separates roxadustat from erythropoiesis-stimulating agents (ESAs), the current standard of care.”
“We are pleased with the growing body of data that we continue to observe from our roxadustat studies, which repeatedly show this agent to be well tolerated and to demonstrate the ability to maintain hemoglobin levels in multiple types of CKD patients being treated for anemia, including patients non-responsive to ESAs, such as those deemed hyporesponsive due to inflammation. In this study in particular, we observed that roxadustat dose requirements did not increase in proportion to CRP levels,” said Thomas B. Neff, chief executive officer of FibroGen. “Given the promising data we have seen to date, we, along with our partners, continue to advance our roxadustat global Phase 3 clinical program evaluating the efficacy and safety of roxadustat in patients with anemia due to CKD.”
About the Study
This was a randomized, open-label, active-comparator study in dialysis patients who previously had hemoglobin (Hb) levels maintained with epoetin alfa. This study was conducted in 144 patients who received roxadustat or epoetin alfa for a period of six weeks in part one or 19 weeks in part two. Eligible patients were aged 18 to 75 years and receiving maintenance hemodialysis thrice weekly for four or more months. Hb levels were 9.0 to 13.5 g/dL for eight weeks, and patients had stable epoetin alfa dosages of < 450 U/kg/wk for four weeks prior to randomization. Roxadustat was dosed orally three times weekly. Initial dosing cohorts ranged between 1.0 – 2.0 mg/kg per dose fixed irrespective of weight and tiered weight based dosing strategies.
Roxadustat was well tolerated in the study population. Treatment-emergent adverse events were reported in 63 percent of all patients in the safety population. The nature and severity of the adverse events was typical for patients undergoing dialysis.
About Roxadustat (FG-4592)
Roxadustat is currently in Phase 3 development as a potential therapy for anemia associated with chronic kidney disease in both patients on dialysis and not on dialysis. Roxadustat is an orally administered small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase activity. 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.
AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat (FG-4592) for the treatment of anemia in patients with CKD in the U.S., China, and other markets. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat in Europe, Japan, the Commonwealth of Independent States, the Middle East, and Africa. For information about roxadustat studies that are currently recruiting patients, please visit clinicaltrials.gov at this link: https://clinicaltrials.gov/ct2/results?term=roxadustat&Search=Search.
About Chronic Kidney Disease
Chronic kidney disease (CKD) affects more than 200 million people worldwide and more than 30 million adults in the U.S. Although it can occur at any age, it becomes more common in aging populations and the prevalence is increasing. Anemia is a common complication of CKD and is associated with significant morbidity and mortality in dialysis and non-dialysis populations. In addition, CKD can be both a cause and a consequence of cardiovascular disease and is now a critical worldwide healthcare issue that represents a large and growing unmet medical need. Currently, no curative treatment or ability to stop kidney deterioration in patients with CKD exists with the exception of kidney transplantation.
About FibroGen
FibroGen is a research-based biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics to treat serious unmet medical needs. The company utilizes its extensive experience in fibrosis and hypoxia-inducible factor (HIF) biology to generate development programs in multiple therapeutic areas. Its most advanced product candidate, roxadustat, or FG-4592, is an oral small molecule inhibitor of HIF prolyl hydroxylases, or HIF-PHs, in Phase 3 clinical development for the treatment of anemia in CKD. A second product candidate, FG-3019, is a monoclonal antibody in Phase 2 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), pancreatic cancer, and liver fibrosis. For more information please visit: www.fibrogen.com.
Forward-Looking Statements
This release contains forward-looking statements, including statements regarding the tolerability of roxadustat, the potential ability of roxadustat to maintain anemia correction without ongoing intravenous iron repletion, the potential ability of roxadustat to maintain hemoglobin levels in multiple types of CKD patients being treated for anemia, the potential ability of roxadustat to treat inflamed patients, and the potential for continued safety or efficacy in our Phase 3 studies. Our actual results may differ materially from these early data and any forward-looking statements due to risks and uncertainties that are described in our Annual Report on Form 10-K and our quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release and we undertake no obligation to update any forward-looking statement in this press release, except as required by law.
Contact: Leanne C. Price FibroGen, Inc. lprice@fibrogen.com 415.978.1200
