- AstraZeneca and partner Fibrogen's experimental drug roxadustat is as safe for the heart as placebo in chronic kidney disease patients who do not require dialysis and safer than epoetin alfa on a five-point measure of cardiovascular complications in patients who require dialysis, the companies said Friday.
- The announcement at the American Society of Nephrology meeting cleared up months of confusion over roxadustat's cardiac safety following a May update when Fibrogen's executive team wasn't able to clearly say regulators would view it as being at least as safe as placebo and epoetin.
- Shares in San Francisco-based Fibrogen rose 8% following the news but have not returned to the levels seen before the company's first data announcement.
Anemia is a side effect of chronic kidney disease and is made worse because of blood loss during dialysis. Erythropoietin-stimulating agents, or ESAs, are prescribed for patients to correct anemia, but regulators have become more conservative because of the risk of cardiovascular side effects if patient hemoglobin levels rise too high.
AstraZeneca and Fibrogen need to prove that roxadustat, which stimulates red-blood-cell production by modulating a biological pathway that responds to lower oxygen concentrations, didn't increase the risk of cardiovascular complications or death. In non-dialysis patients, who are less likely to receive ESAs, that meant showing roxadustat was at least as safe as placebo, while for those on dialysis, roxadustat's safety was compared to epotein alfa.
Pooled data from nearly 10,000 patients across seven trials confirmed that finding.
The companies' analysis revealed a slightly higher numerical risk for non-dialysis dependent patients treated with roxadustat compared to placebo, but that did not clear a threshold for statistical significance on all three endpoints examined. Two of those were measures capturing cardiovascular complications plus death while the third looked at death by any cause.
Compared with patients taking epoetin alfa in the dialysis population, the roxadustat patients were 14% less at risk of suffering one of four heart complications or death and were at a statistically equal risk on a narrower heart measure and on all cause mortality alone.
A third group of patients who had begun dialysis in the preceding four months were at a 30% lower risk of major adverse cardiac events and 34% lower risk on the broader heart outcome measure if they took roxadustat instead of epoetin. There was no difference on death by any cause.
Leerink's Geoffrey Porges called the pooled results the "best case outcome" for Fibrogen and roxadustat, "particularly given the confusion that prevailed after the company's initial announcement of the results earlier this year."
The two companies expect to submit these data as part of their application for Food and Drug Administration approval before the end of the year. Roxadustat is already on the market in Japan for dialysis patients under the brand name Evrenzo, and for both patient groups in China.
AstraZeneca and Fibrogen share responsibility for roxadustat's development and commercialization in the U.S. and China. In Japan, Fibrogen is working with the drugmaker Astellas Pharma.
Correction: A previous version of this article misstated in which countries AstraZeneca and Fibrogen collaborate.