AstraZeneca (AZN) and FibroGen Inc. (FGEN) Roxadustat Phase III Program Pooled Analyses Showed Positive Efficacy and No Increased Cardiovascular Risk in Patients with Anemia from Chronic Kidney Diseas
AstraZeneca (NYSE: FGEN) and FibroGen Inc. (FibroGen) (Nasdaq: FGEN) today presented pooled efficacy and cardiovascular (CV) safety analyses from the pivotal Phase III program assessing roxadustat for the treatment of patients with anemia from chronic kidney disease (CKD).
The pooled CV safety analyses showed that roxadustat, an oral investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), did not increase the risk of MACE, MACE+ and all-cause mortality in non dialysis-dependent (NDD) compared to placebo and dialysis-dependent (DD) patients compared to epoetin alfa, a current medicine used to treat anemia.
In a clinically important predefined subgroup of incident dialysis (ID) patients, defined as patients who have been on dialysis for four months or less, roxadustat reduced the risk of MACE and MACE+ and showed a trend towards lower risk of all-cause mortality relative to epoetin alfa.
Key safety endpoints consisted of time to major adverse CV events (MACE), defined as all-cause mortality, stroke and myocardial infarction, and time to MACE+, defined as MACE, unstable angina requiring hospitalization and congestive heart failure requiring hospitalization.
The results were presented in an oral late-breaking abstract session at the American Society of Nephrology (ASN) Kidney Week 2019 in Washington, D.C.
Mene Pangalos, Executive Vice President, BioPharmaceuticals, R&D, said: “These highly anticipated results reinforce our confidence in the potential of roxadustat to address significant unmet medical needs among patients with anemia from chronic kidney disease, particularly for those who have recently started dialysis. The pooled analyses showed incident dialysis patients receiving roxadustat had a lower risk of cardiovascular events which is important as these patients may experience higher rates of morbidity and mortality than those on stable dialysis.”
Robert Provenzano, MD, Associate Professor of Medicine, Wayne State University, Detroit, Michigan, US and a primary investigator on the global Phase III program, said: “In the US, roxadustat has the potential to be the first in a new class of medicines for the treatment of anemia from chronic kidney disease. This pooled cardiovascular safety data, together with strong efficacy data, support its potential as an important new treatment option for patients with anemia from chronic kidney disease who have seen little to no innovation in decades.”
Key headline data from the roxadustat Phase III program pooled CV safety analyses
Population Comparator |
| MACE |
| MACE+ |
| All-cause mortality |
| Conclusion |
NDD (n=4,270)
Placebo | HR 1.08 (95% CI, 0.94, 1.24)
| HR 1.04 (95% CI, 0.91, 1.18)
| HR 1.06 (95% CI, 0.91, 1.23)
| The risk of MACE, MACE+ and all-cause mortality in roxadustat patients was comparable to placebo | ||||
IDi,ii (n=1,526)
Epoetin alfa | HR 0.70 (95% CI, 0.51, 0.96)
| HR 0.66 (95% CI, 0.50, 0.89)
| HR 0.76 (95% CI, 0.52, 1.11)
| In ID patients, those taking roxadustat had a 30% lower risk of MACE and 34% lower risk of MACE+ compared to those taking epoetin alfa, with a trend towards lower all-cause mortality for roxadustat relative to epoetin alfa | ||||
DD (n=3,880)
Epoetin alfa | HR 0.96 (95% CI, 0.82, 1.13)
| HR 0.86 (95% CI, 0.74, 0.98)
| HR 0.96 (95% CI, 0.79, 1.17)
| No increased risk of MACE and all-cause mortality and a lower risk of MACE+ compared to epoetin alfa |
- ID patients are those who initiated dialysis within four months prior to randomization
- ID patients are a subgroup of the DD patient population
The primary efficacy endpoint was achieved in the pooled analyses for NDD and DD patients, and in all individual Phase III trials. Data from the pooled efficacy and CV safety analyses, together with other statistical analyses, will form part of the regulatory submission in the US, which is anticipated in Q4 2019.
The pooled efficacy analyses in the NDD population showed roxadustat demonstrated a statistically significant mean increase from baseline in hemoglobin (Hb) levels, regardless of iron repletion, averaged over weeks 28 to 52 of 1.85 g/dL in patients treated with roxadustat compared to 0.13 g/dL with placebo (p<0.001).
The pooled efficacy analyses in the DD population showed roxadustat demonstrated a statistically significant mean increase from baseline in Hb levels averaged over weeks 28 to 52 with 1.22 g/dL in patients treated with roxadustat compared to 0.99 g/dL with epoetin alfa (p<0.001).
About roxadustat
Roxadustat is an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has the potential to promote erythropoiesis by increasing endogenous production of erythropoietin and improving iron regulation and overcoming the negative impact of inflammation on hemoglobin synthesis and red blood cell production resulting in a downregulation of hepcidin. Use of roxadustat may coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range, in multiple subpopulations of CKD patients, including in the presence of inflammation.