FibroGen, Inc., announced the publication of positive clinical data examining roxadustat, an orally administered small molecule inhibitor of hypoxia-­inducible factor (HIF) prolyl hydroxylase activity, as a potential anemia treatment in patients with chronic kidney disease (CKD).

The data appeared in the study, “Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study,”  published in the American Journal of Kidney Disease.

Data from the randomized, open-label, active-comparator Phase 2 clinical trial, conducted in 144 dialysis patients who previously had hemoglobin (Hb) levels maintained with epoetin alfa, showed that three times weekly treatment with roxadustat maintained hemoglobin levels — irrespective of baseline iron repletion status, degree of inflammation (CRP) or earlier iron regimen — over six and 19 weeks of treatment.

The primary endpoint was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1), and as mean Hb level ≥ 11.0g/dL during the last four weeks of treatment (part 2).

In part 1 of the trial, roxadustat was administered to patients for a period of six weeks in its lowest dose levels (1.0 mg/kg per dose thrice weekly, TIW). The results showed that this treatment maintained hemoglobin at a level comparable to epoetin alfa (44% versus 33%).  Roxadustat administered at doses of 1.5 mg/kg or more reached superior Hb response compared with epoetin alfa (79% versus 33%).

In part 2 of the trial, the difference in the levels of hemoglobin in patients who received roxadustat and those who received epoetin alfa was of -0.03 g/dL. In terms of the trial’s primary endpoint, results showed that 51% of the patients who received roxadustat achieved a level of Hb of > 11.0 g/dL over the final four weeks of the 19 weeks of treatment, compared with 36% of patients receiving epoetin alfa.

During the last seven weeks of treatment, the dose requirements of roxadustat maintenance were not correlated with levels of the inflammatory parameter CRP, even in those patients who had elevated CRP levels.

Results also revealed that hemoglobin was maintained within physiologic levels of endogenously produced erythropoietin in patients treated with roxadustat, who were tested while reticulocytes were produced and continued to exhibit stable concentrations of hemoglobin in the absence of intravenous iron .

Roxadustat significantly reduced mean total cholesterol levels and hepcidin, results not observed with epoetin alfa. No safety concerns were raised.

“This trial showed that conversion to roxadustat from epoetin alfa to treat end-stage renal disease patients on dialysis can be successfully accomplished.  The potential ability of roxadustat to treat inflamed patients, a vulnerable population, removing the need for exposure to high erythropoietin levels, is particularly fascinating,” Robert Provenzano, MD, the study’s lead author and chief of the Division of Nephrology, Hypertension & Transplantation, director of Nephrology Research, and director of Acute Dialysis Services at St. John Hospital and Medical Center in Detroit, Michigan, said in a press release. “The potential ability of roxadustat to maintain anemia correction without ongoing intravenous iron repletion separates roxadustat from erythropoiesis-stimulating agents (ESAs), the current standard of care.”

Roxadustat is now in Phase 3 testing as a potential therapy for anemia associated with chronic kidney disease in both patients on and off dialysis.

“We are pleased with the growing body of data that we continue to observe from our roxadustat studies, which repeatedly show this agent to be well tolerated and to demonstrate the ability to maintain hemoglobin levels in multiple types of CKD patients being treated for anemia, including patients non-responsive to ESAs, such as those deemed hyporesponsive due to inflammation.  In this study in particular, we observed that roxadustat dose requirements did not increase in proportion to CRP levels,” said Thomas B. Neff, chief executive officer of FibroGen. “Given the promising data we have seen to date, we, along with our partners, continue to advance our roxadustat global Phase 3 clinical program evaluating the efficacy and safety of roxadustat in patients with anemia due to CKD.”