- Fibrogen released data from seven trials of roxadustat for treatment of anemia in kidney disease that it says shows it causes no more cardiovascular complications than Epogen in patients on dialysis. Company executives could not say, however, whether the Food and Drug Administration would agree with its analysis.
- Fibrogen's release shook investors, who drove down shares 24% in trading Friday. Analysts characterized Fibrogen's description as confusing, but reaffirmed their evaluation that roxadustat will receive FDA approval.
- Epogen and other biological agents that stimulate red blood cell production raise the risk of heart attacks and strokes, and their use is tightly controlled. Physicians and regulators want alternatives, something Fibrogen hopes roxadustat can be.
Anemia is a common complication of chronic kidney disease, and it can be made worse by hemodialysis. Physicians have treated it for some time with the use of Amgen's Epogen (epoetin alfa) and other erythropoiesis-stimulating agents (ESAs).
However, increasing hemoglobin levels to near-normal levels led to an increase in cardiovascular complications, so the FDA tightened its prescribing advice to keep hemoglobin levels lower, and also launched a search for a safer alternative.
Fibrogen and rival Akebia Therapeutics each came up with what they hope to be one alternative, using a biological pathway that mimics the body's response to being exposed to lower oxygen air at high altitudes. These experimental hypoxia-inducible factor prolyl hydroxylase inhibitors, roxadustat and vadadustat, aim to stimulate the body's endogenous erythropoietin, and have the advantage of being oral rather than infused intravenously as with the ESAs.
To pass the regulators, however, roxadustat and vadadustat will need to show that they are at least as safe as ESAs.
Fibrogen and partner AstraZeneca had roxadustat in seven safety trials encompassing more than 8,000 patients. The studies evaluated major adverse cardiovascular events in patients on dialysis and before they'd progressed. In the dialysis patients, roxadustat was compared with Epogen and in the pre-dialysis it was compared with placebo, as ESAs are not commonly used in this population.
Fibrogen's vague description of the results shook investors, specifically when it described roxadustat as showing "no clinically meaningful difference" with Epogen and placebo in their respective trials on heart attacks, strokes and death.
When pressed on this description in a conference call, Thomas Neff, Fibrogen's chief executive officer, said the company and the FDA had not agreed on what constituted "non-inferiority," a statistically rigorous way of evaluating whether two agents are equally safe. This statement opens the possibility that further analysis could reveal roxadustat to be less safe.
However, K. Peony Yu, the company's chief medical officer, said Fibrogen's analysis revealed that roxadustat had met a common standard for showing non-inferiority.
Fibrogen also was keen to play up the results in a pre-specified group of 1,500 patients who have just begun dialysis, which it believes to be the most likely target population for roxadustat. In these patients, roxadustat showed statistical superiority to Epogen.
AstraZeneca and Fibrogen expect to submit roxadustat to the FDA for approval in the second half of 2019.