November 4, 2007
American Society of Nephrology (ASN) Renal Week 2007, San Francisco, CA
Abstract SU-PO806

Preliminary Results from a Randomized, Single-Blind, Placebo-Controlled Trial of FG-4592, a Novel Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor, in Subjects with CKD Anemia. PA Frohna, S Milwee, J Pinkett, T Lee, K Moore-Perry, J Chou, RH Ellison.

FibroGen Inc., San Francisco, CA, United States.

Background: FG-4592 is an oral inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase in clinical development for the treatment of anemia. Stabilization of HIF, a cytosolic transcription factor, by FG-4592 leads to activation of the genes associated with erythropoiesis, including EPO and enzymes involved in iron metabolism.

Study Design: A randomized, single-blind, placebo-controlled, 4-week study of oral doses of FG-4592 (1 to 4 mg/kg) administered 2 or 3 times weekly. The objectives of this study were to characterize the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of FG-4592 in subjects with CKD anemia. Thirty subjects were to be enrolled into 2 cohorts at each dose: Pharmacokinetic (PK, n=12, Hb<13 g/dL) and Treatment (TX, n=18, Hb<11 g/dL). All subjects were monitored for safety, including vital signs, clinical labs, and adverse events during treatment and for 4 weeks thereafter.

Results: Data from the 1 mg/kg cohort (21 active- and 8 placebo-treated) demonstrate that FG-4592 doses up to 120 mg are considered generally well-tolerated, with treatment emergent AEs attributed to study drug reported from only 2 subjects (1 active and 1 placebo). No clinically significant changes in serum chemistry or vital signs were observed in any subjects. Multiple samples from the PK subjects were collected and used to measure FG-4592 and circulating endogenous EPO levels. FG-4592 was rapidly absorbed with a mean Tmax= 1.8 hrs, mean Cmax= 5.9 µg/mL, and mean half-life= 11 hrs, which were comparable after the first and last dose, and similar to those previously observed in healthy subjects. Median peak plasma EPO levels of 115 mIU/mL occurred 8-12 hrs post-dose, and were comparable for first and last dose. In the TX group, 5 of 13 subjects (38%) treated with FG-4592 had increases in Hb≥1 g/dL during the 4-week treatment period, and maintained that increase for 2-4 wks after stopping treatment. None of 4 placebo subjects had a similar Hb increase. In conclusion, 4 weeks of treatment with FG-4592 was well-tolerated and produced significant Hb increases in some subjects with CKD anemia.

See also November 7, 2007 press release