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Roxadustat demonstrates non-inferiority to darbepoetin alfa in achievement of Hb correction in DOLOMITES Phase 3 study of anemia in non-dialysis dependent patients with chronic kidney disease
SAN FRANCISCO, June 08, 2020 (GLOBE NEWSWIRE) -- FibroGen, Inc. (FGEN) announced data from three roxadustat clinical trials, including the Phase 3 DOLOMITES study evaluating roxadustat for treatment of anemia in non-dialysis-dependent CKD patients compared to darbepoetin alfa, and ophthalmology findings from a Japan Phase 3 study evaluating roxadustat compared to darbepoetin alfa in patients on hemodialysis 1. These data were presented in virtual oral sessions of the 57th European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Virtual Congress, taking place June 6 - 9, 2020. These trials were conducted by Astellas Pharma, Inc., FibroGen’s collaboration partner for roxadustat in Europe, Japan and certain other markets.
The Phase 3 DOLOMITES study evaluated the efficacy and safety of roxadustat compared to darbepoetin alfa for the treatment of anemia in non-dialysis dependent (NDD) patients with stage 3 - 5 chronic kidney disease (CKD). In the primary endpoint analysis, the study demonstrated non-inferiority of roxadustat to darbepoetin alfa in the proportion of patients achieving correction of hemoglobin (Hb) levels during the first 24 weeks of treatment (89.5% vs 78.0%; a difference of 11.51% [95% confidence interval (CI): 5.66%, 17.36%]), with a lower bound of 95% confidence interval >0%. The response in correction of hemoglobin levels was defined as achieving Hb ≥11g/dL and Hb increase from baseline of ≥1g/dL with baseline Hb >8g/dL, or Hb increase from baseline of ≥2.0 g/dL in patients with baseline Hb ≤8.0 g/dL.
Secondary endpoints were hierarchically tested for non-inferiority and superiority. Roxadustat was superior to darbepoetin alfa in decreasing low-density lipoprotein cholesterol with a least square mean (LSM) difference of -0.403 mmol/L (95% CI -0.510, -0.296; [P<0.01]) and superior in time to first intravenous iron use with a hazard ratio (HR) of 0.45 (95% CI: 0.26, 0.78; [P=0.004]). The non-inferiority of roxadustat to darbepoetin alfa on hypertension risk was demonstrated for mean arterial pressure change from baseline to weeks 12-28 with a LSM difference of -0.372 mmHg (95% CI: -1.587, 0.842) and time to occurrence of hypertension HR 0.83 (95% CI: 0.56, 1.22). Regarding safety, the overall incidence of treatment-emergent adverse events was comparable between roxadustat and darbepoetin alfa (91.6% and 92.5%, respectively).
With a relatively small sample size (roxadustat n=323, darbepoetin n=293), non-confirmatory analysis of adjudicated major adverse cardiovascular events (MACE), and MACE plus hospitalized unstable angina and hospitalized congestive heart failure (MACE+) outcomes showed HR point estimates of 0.81 (95% CI: 0.52, 1.25) and 0.90 (95% CI: 0.61, 1.32).
“The goal of treatment for anemia in CKD is to ensure sufficient oxygenation to vital organs in the body. The vast majority of CKD patients, however, continue to suffer from moderate to severe anemia with low hemoglobin levels which are associated with a higher risk of blood transfusions and with debilitating symptoms that can make daily activities extremely challenging,” said K. Peony Yu, M.D., Chief Medical Officer, FibroGen. “The results for roxadustat presented at this year’s ERA-EDTA meeting represent the breadth of our clinical development program and our commitment to the continued evaluation of roxadustat as a potential treatment for anemia in chronic kidney disease across a spectrum of patients and treatment settings.”
“The DOLOMITES data adds to the comprehensive body of evidence supporting the safety and efficacy of roxadustat in adult chronic kidney disease patients with anemia who are non-dialysis dependent (NDD),” said Enrique Conterno, Chief Executive Officer, FibroGen. “The studies presented at the ERA-EDTA Virtual Congress 2020 reinforce our commitment to turning innovative science into valued therapeutic medicines for patients.”
Ophthalmological effects of roxadustat from a Phase 3, randomized, double-blind, active-comparator study in Japanese patients on dialysis converted from ESA therapy (Study 1517-CL-307) 2 were also presented at the ERA-EDTA Virtual Congress 2020. The primary endpoint of the study was achieved as roxadustat maintained hemoglobin within 10–12 g/dL in patients on hemodialysis and was non-inferior to darbepoetin alfa. Treatment-emergent adverse events were consistent with previous reports and overall study results were recently published in the Journal of the American Society of Nephrology. This presentation at ERA-EDTA focused on a prospective analysis of ophthalmological/retinal-related events observed during this Phase 3 study. During the 24-week treatment period, these data suggest that dialysis dependent CKD patients who were treated with roxadustat were not at an increased risk of ophthalmic abnormalities, compared with patients treated with darbepoetin alfa. This includes retinal hemorrhages or increased retinal thickness.
About the DOLOMITES Trial (Abstract MO001)
DOLOMITES is a Phase 3, randomized, open-label, active-controlled study to evaluate the efficacy and safety of roxadustat in comparison to darbepoetin alfa in the treatment of anemia in adult NDD CKD patients. The study enrolled 616 adult anemia patients with stage 3-5 CKD, of which 323 received roxadustat and 293 received darbepoetin alfa. The response in correction of hemoglobin levels was defined as achieving Hb ≥11g/dL and Hb increase from baseline of ≥1g/dL with baseline Hb >8g/dL, or Hb increase from baseline of ≥2.0 g/dL in patients with baseline Hb ≤8.0 g/dL. For more information about this study, visit www.clinicaltrials.gov [NCT02021318].
About Study 1517-CL-0307 (Abstract MO002)
Study 1517-CL-0307 is a Phase 3, randomized, double-blind, active-controlled clinical trial, conducted at 58 Japanese sites to evaluate the non-inferiority of roxadustat to darbepoetin alfa when both drugs are titrated to maintain Hb levels of 10-12g/dL in Japanese CKD patients on hemodialysis. The study randomized 303 patients to receive either roxadustat (n=151) or darbepoetin alfa (n=152) for 24 weeks. The safety of roxadustat was assessed by monitoring treatment emergent adverse events and through detailed ophthalmologic investigations, including adjudicated examination of retinal vascular findings before and after treatment. For more information about this study, visit www.clinicaltrials.gov. [NCT02952092].
About Anemia Associated with CKD
Chronic kidney disease (CKD) is generally a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure or end stage renal disease, requiring dialysis or kidney transplant. CKD is estimated to occur in approximately 10-12% of adults worldwide3 and is predicted to become the fifth most common cause of premature death globally by 2040.4
Anemia, a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin, is a common early complication of CKD,5 affecting approximately 20% of CKD patients.6 Anemia in CKD is associated with an increased risk of hospitalization, cardiovascular complications and death, and can also cause significant fatigue, cognitive dysfunction and reduced quality of life. Blood transfusions are used for treating severe anemia, however, they may reduce a patient’s opportunity for kidney transplant and can increase the risk of infection and/or complications such as heart failure and allergic reactions.
Roxadustat is a first-in-class, orally administered small molecule HIF-PH inhibitor that promotes erythropoiesis through increasing endogenous production of erythropoietin, and improved iron absorption, transport and mobilization. Roxadustat is approved in China for the treatment of anemia in CKD patients on dialysis and patients not on dialysis, and is approved in Japan for the treatment of anemia in CKD patients on dialysis, and a supplemental NDA for the treatment of anemia in CKD patients not on dialysis is under regulatory review. The roxadustat NDA for the treatment of anemia in CKD is under review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act date of December 20, 2020. The Marketing Authorization Application for roxadustat for the treatment of anemia in CKD was filed by our partner Astellas and accepted by the European Medicines Agency for review on May 21, 2020. Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anemia.
Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in territories including Japan and Europe. AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in the U.S., China, and other markets.
FibroGen, Inc. is a biopharmaceutical company committed to discovering, developing and commercializing a pipeline of first-in-class therapeutics. The company applies its pioneering expertise in hypoxia-inducible factor (HIF) and connective tissue growth factor (CTGF) biology to advance innovative medicines to treat unmet needs. The Company is currently developing and commercializing roxadustat, an oral small molecule inhibitor of HIF prolyl hydroxylase activity, for anemia associated with chronic kidney disease (CKD). Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anemia. Pamrevlumab, an anti-CTGF human monoclonal antibody, is in clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), locally advanced unresectable pancreatic cancer, and Duchenne muscular dystrophy (DMD). For more information, please visit www.fibrogen.com.
This release contains forward-looking statements regarding our strategy, future plans and prospects, including statements regarding the development and commercialization of the company’s product candidates, the potential safety and efficacy profile of our product candidates, our clinical programs and regulatory events, and those of our partners. These forward-looking statements include, but are not limited to, statements about our plans, objectives, representations and contentions and are not historical facts and typically are identified by use of terms such as “may,” “will”, “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. Our actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of our various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in our Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and our Quarterly Report on Form 10-Q for quarter ended March 31, 2020 filed with the Securities and Exchange Commission (SEC), 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.
Michael Tung, M.D.
Clinicaltrials.gov. Roxadustat in the Treatment of Anemia in Chronic Kidney Disease (CKD) Patients, Not on Dialysis, in Comparison to Darbepoetin Alfa (Dolomites). Available from: https://clinicaltrials.gov/ct2/show/NCT02021318 [Last accessed: June 2020].
Clinicaltrials.gov. A Phase 3, Multi-center, Randomized, 2-arm Parallel, Double-blind, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia. Available from: https://clinicaltrials.gov/ct2/show/NCT02952092 [Last accessed: June 2020].
International Society of Nephrology. Chronic kidney disease. Global kidney health atlas. Available from: www.theisn.org/global-atlas [Last accessed: January 2020].
Institute for Health Metrics and Evaluation (IHME). Findings from the Global Burden of Disease Study 2017. Seattle, WA: IHME, 2018. Available from: http://www.healthdata.org/sites/default/files/files/policy_report/2019/GBD_2017_Booklet.pdf [Last accessed: January 2020].
McClellan W, Aronoff SL, Bolton WK, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin 2004;20:1501–1510.
Dmitrieva O, de Lusignan S, Macdougall IC, et al. Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data. BMC Nephrol 2013;14:24.