Roxadustat (FG-4592): Correction of Anemia in Incident... : Journal of the American Society of Nephrology (original) (raw)

Clinical Research

Correction of Anemia in Incident Dialysis Patients

Besarab, Anatole*; Chernyavskaya, Elena†; Motylev, Igor‡; Shutov, Evgeny§; Kumbar, Lalathaksha M.‖; Gurevich, Konstantin¶; Chan, Daniel Tak Mao**; Leong, Robert*; Poole, Lona*; Zhong, Ming*; Saikali, Khalil G.*; Franco, Marietta*; Hemmerich, Stefan*; Yu, Kin-Hung Peony*; Neff, Thomas B.*

*FibroGen, Inc., San Francisco, California;

†Budgetary Healthcare Institution of Omsk Region, City Clinical Hospital #1, Omsk, Russia;

‡City Hospital #33, Nizhny Novgorod, Russia;

§State Budgetary Healthcare Institution of Moscow, City Clinical Hospital, Moscow, Russia;

‖Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan;

¶Fresenius Medical Care, St. Petersburg, Russia; and

**Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

Correspondence: Dr. Anatole Besarab, FibroGen, Inc., 409 Illinois Street, San Francisco, CA. [email protected]

Received March 4, 2015

Accepted June 29, 2015

Abstract

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 (_Δ_Hbmax), 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, _Δ_Hbmax 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.