The decision follows an advisory committee recommendation not to approve because of safety issues.
FibroGen has received a Complete Response Letter from the FDA for roxadustat for the treatment of anemia of chronic kidney disease (CKD). The agency has requested that an additional clinical study of roxadustat be conducted prior to resubmission.
The response letter comes after a July decision by the Cardiovascular and Renal Drugs Advisory Committee to not recommend approval of roxadustat. Panelists cited safety issues in two votes against approval: 12-2 vote on roxadustat as a treatment for patients who are on dialysis and 13-1 vote on the drug as a treatment for patients who not on dialysis.
Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is being developed to treat anemia in patients with CKD. HIF-PHI drugs aim to restore production of the hormone erythropoietin and improve iron regulation. Currently, the condition is treated by injections of epoetin alpha and darbepoetin alpha.
Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes and for chemotherapy-induced anemia.
“We are deeply disappointed with this result, and this is an unfortunate day for patients suffering from anemia of CKD in the United States,” Enrique Conterno, chief executive officer, FibroGen, said in a statement. “Roxadustat is changing the lives of patients around the world, and we and our partner AstraZeneca will discuss next steps in the United States.”
This application has had a rocky journey. Fibrogen submitted the NDA for roxadustat tablets in December 2019. The PDUFA date was March 20, 2021, which was already an extension from the original PDUFA date of December 20, 2020. PDUFA dates are deadlines for the FDA to review the applications of new drugs
According to documents from the FDA ahead of the advisory committee meeting, agency officials believed the data showed roxadustat demonstrated efficacy. The concern, agency official said, was the hemoglobin overcorrection especially in nondialysis-dependent patients. Although the data submitted by FibroGen demonstrated roxadustat was effective in increasing hemoglobin levels, the drug tends to overshoot targets in patients who are non-dialysis-dependent.
In data previously released by the company, a commonly used composite end point of major adverse cardiovascular events (MACE) was the primary safety endpoint agreed on with the FDA. FibroGen argues that roxadustat is comparable to placebo in nondialysis dependent patients and to epoetin-alfa in dialysis dependent patients using MACE to measure cardiovascular safety.