FDA Panel Votes Against Roxadustat, Cites Risk of Thrombotic Events

The US Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against recommending approval of roxadustat for the treatment of anemia in adult patients with chronic kidney disease (CKD), regardless of whether or not they were on dialysis.

The committee voted 13-1 against the approval for treatment of chronic kidney disease in patients not on dialysis (NDD) and 12-2 against the approval for patients on dialysis (DD), citing concerns over an increased risk for thrombotic events and other major cardiovascular adverse events.

“New solutions are needed for the six million people in the US affected by anemia of chronic kidney disease. Although we are disappointed by today’s outcome, we will continue to work closely with our partner FibroGen and the FDA to determine the path forward for roxadustat,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, in a statement from AstraZeneca, who is developing the agent in collaboration with FibroGen Inc and Astellas Pharma Inc.

“While we are disappointed with today's outcome,” said Enrique Conterno, Chief Executive Officer of FibroGen, in a statement. “We believe the scientific evidence supports roxadustat approval in the U.S. and will work with the FDA as it completes its review of the New Drug Application for roxadustat.”

An oral, small molecule, hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, roxadustat was the first HIF-PH inhibitor to be accepted by the FDA for review in treatment of anemia in patients with CKD. Evaluated in a phase 3 program including more than 8000 patients and half a dozen trials, data behind roxadustat has warranted approval in other countries such as China, Japan, Chile, and South Korea for treatment of anemia in CKD in NDD and DD patients. The agent is also under final regulatory review with the European Medicines Agency.

“The sponsor has done its clinical trials with a very specific strategy but now would like approval for a strategy which has been developed only as a simulation. If they really want people to use the new strategy in clinical practice, they really do need to test it and show its efficacy and safety,” said Milton Packer, MD, FDA CRDAC committee member and cardiologist at Baylor Medical Center, after voting against recommending approval for treatment of anemia due to CKD in NDD.