×

Phase 2 Data for Investigational Orally Active HIF-PHI Roxadustat (FG-4592) Show Anemia Correction in Incident Dialysis Chronic Kidney Disease Patients Regardless of Iron Repletion Status, Iron Supplementation Regimen, or Dialysis Modality

SAN FRANCISCO, Oct. 22, 2015 (GLOBE NEWSWIRE) -- FibroGen, Inc. (Nasdaq:FGEN) (“FibroGen”), a research-based biopharmaceutical company, along with its partner, AstraZeneca (NYSE:AZN), today announced that the Journal of the American Society of Nephrology has published Phase 2 data showing roxadustat, an investigational therapy for the treatment of anemia in patients with chronic kidney disease (CKD), achieved 96 percent hemoglobin (Hb) response and increased mean Hb regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality within 7 weeks.

The primary endpoint, the mean maximum Hb change from baseline (baseline Hb 8.3+1.0 g/dL), was 3.1 ±0.2 g/dL (SEM) among the efficacy evaluable subjects (n=55). Hb response, defined as Hb increase by ≥ 1.0 g/dL, was achieved in 96 percent of all roxadustat-treated subjects, with a median time to Hb response of 3 weeks in each cohort.

“This trial demonstrated that roxadustat may be able to correct anemia in an incident dialysis population, and to do so with either oral or IV iron supplementation even when the patient’s initial iron status does not meet broadly accepted clinical practice guidelines,” said Anatole Besarab, MD, executive director, clinical research, at FibroGen, and lead author. “The correction of anemia with roxadustat did not require prior iron repletion as is often the case with erythropoiesis-stimulating agents. This independence of hemoglobin response from iron regimen or basal iron status resulted from reduction in the hepcidin levels.”

The rates of increase in mean Hb over the 12-week treatment period and the mean Hb levels during the last four weeks were similar among patients receiving oral or intravenous (IV) iron (mean maximum Hb change of 3.4 to 3.5 g/dL). Roxadustat therapy in the absence of any form of iron supplementation still led to a mean maximum Hb increase of 2.8 g/dL.

“We designed this study to evaluate the ability of roxadustat to correct hemoglobin in what is widely regarded as the highest risk yet least frequently studied population of CKD patients,” said Thomas Neff, chief executive officer of FibroGen. “Our study showed that newly initiated dialysis patients with end stage renal disease had a robust hemoglobin response regardless of whether they received IV or oral iron supplementation. FibroGen and its partners are currently conducting a global Phase 3 clinical program evaluating the efficacy and safety of roxadustat in patients with anemia due to CKD, including incident and stable dialysis patients and patients not on dialysis.”

Current treatment of anemia in CKD requires erythropoiesis-stimulating agents (ESAs) with IV iron supplementation, particularly in end stage renal disease patients (ESRD). In standard clinical practice, ESRD patients who have recently started dialysis are a clinically challenging population. During the first four months of dialysis initiation, life-threatening cardiovascular complications and other adverse events generally occur more frequently than thereafter, leading to a higher mortality rate for incident dialysis patients than for stable dialysis patients.1 It is during this period of initiation that the highest doses of erythropoietin analog and IV iron use are required. In addition, a variety of factors, including the obligate need for IV iron with ESAs, inhibit optimal Hb correction during this initiation period.2

About the Study
This was a randomized, open-label, dose-titration study in incident dialysis subjects not receiving ESA treatment to evaluate the efficacy of roxadustat in the correction of anemia.

This study was conducted in 60 patients who received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks.

Eligible patients were erythropoietin analog-naïve, had initiated dialysis two weeks to four months before enrollment with baseline Hb values ≤10.0 g/dL, had ferritin levels of 50 to 300 ng/mL, had transferrin saturation levels of 10% to 30%, had normal liver function, and had not received IV iron therapy within four weeks prior to randomization. In this study, 24 hemodialysis (HD) subjects received no exogenous iron supplementation, 12 HD and 12 peritoneal dialysis (PD) subjects received oral iron, and 12 HD subjects were administered IV iron.

Roxadustat was dosed orally three times weekly for 12 weeks. Initial doses (1.0 - 1.7 mg/kg per dose) for the first four weeks were determined using three body weight tiers, followed by dose adjustment evaluations every four weeks based on Hb, to a maximum of 2.5 mg/kg.

Roxadustat was well tolerated in the safety population. Treatment-emergent adverse events were reported in 30 patients, 50 percent of all patients in the safety population. The nature and severity of the adverse events was typical for ESRD patients undergoing HD or PD. Adverse events characterized as severe (n=4), life-threatening (n=0), or fatal (n=2) were reported in six (10 percent) patients.

Detailed results and safety data from the trial were published in Journal of the American Society of Nephrology and can be viewed here: http://jasn.asnjournals.org/content/early/2015/10/22/ASN.2015030241.full.pdf+html.

About Roxadustat (FG-4592)
Roxadustat 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. 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.

About 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. Currently, no curative treatment or ability to stop kidney deterioration in CKD exists with the exception of kidney transplantation, creating a significant unmet medical need.

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 orally administered small molecule inhibitor of HIF prolyl hydroxylase (HIF-PH) activity 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 increasing prevalence of CKD and the potential for roxadustat to be able to correct anemia in an incident dialysis population regardless of baseline iron repletion status or method of iron supplementation. Actual prevalence of CKD and our actual results may differ materially from those indicated in these 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.

References

  1. United States Renal Data System. 2013 USRDS annual data report: Epidemiology of kidney disease in the United States, Volume 2, Chapter 5. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013.
  2. United States Renal Data System. 2013 USRDS annual data report: Epidemiology of kidney disease in the United States, Volume 2, Chapter 2. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013.
Contact Greg Mann FibroGen, Inc. 415-978-1433 gmann@fibrogen.com

Source:FibroGen, Inc.