Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.
Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHb(max)), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHb(max) was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.
FibroGen, Inc., San Francisco, California; abesarab@fibrogen.com.
Anatole
A
Besarab
Budgetary Healthcare Institution of Omsk Region, City Clinical Hospital #1, Omsk, Russia;
Elena
E
Chernyavskaya
City Hospital #33, Nizhny Novgorod, Russia;
Igor
I
Motylev
State Budgetary Healthcare Institution of Moscow, City Clinical Hospital, Moscow, Russia;
Evgeny
E
Shutov
Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan;
Lalathaksha M
LM
Kumbar
Fresenius Medical Care, St. Petersburg, Russia; and.
Konstantin
K
Gurevich
Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Daniel Tak Mao
DT
Chan
FibroGen, Inc., San Francisco, California;
Robert
R
Leong
FibroGen, Inc., San Francisco, California;
Lona
L
Poole
FibroGen, Inc., San Francisco, California;
Ming
M
Zhong
FibroGen, Inc., San Francisco, California;
Khalil G
KG
Saikali
FibroGen, Inc., San Francisco, California;
Marietta
M
Franco
FibroGen, Inc., San Francisco, California;
Stefan
S
Hemmerich
FibroGen, Inc., San Francisco, California;
Kin-Hung Peony
KH
Yu
FibroGen, Inc., San Francisco, California;
Thomas B
TB
Neff
D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D006435:Renal Dialysis
D064451:Hepcidins; D007546:Isoquinolines; D005998:Glycine; C584543:roxadustat
anemia; chronic kidney disease; dialysis; erythropoietin