The FDA has issued a complete response letter (CRL) to AstraZeneca and FibroGen stating that an additional clinical trial is needed to support approval of a new drug application (NDA) for roxadustat (Evrenzo) for the treatment of anemia of chronic kidney disease (CKD) in both non-dialysis dependent (NDD) and dialysis-dependent (DD) adult patients.1
The FDA’s decision not to approve roxadustat follows a 13 to 1 vote last month from the agency’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) indicating that the drug’s benefit-risk profile does not support approval for anemia of CKD in adult NDD patients; CRDAC also voted 12 to 2 against approval in adult DD patients.2
At the time of the CRDAC votes against approval, Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca, stated in a press release, “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.”2
The news has not been all negative for AstraZeneca and FibroGen regarding roxadustat. The drug is approved in several countries, included China and Japan, for the treatment of anemia of CKD, and in June 2021, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval of roxadustat for the treatment of adult patients with symptomatic anemia associated with CKD.3
The CHMP based its opinion on a comprehensive package that included data for 9600 patients from a phase 3 program involving 8 multicenter and randomized studies. The trials were conducted at locations worldwide. FibroGen noted in a press release3 at the time of the CHMP recommendation that the robust data demonstrate the efficacy of roxadustat in allowing patients with symptomatic anemia of CKD to reach and sustain target hemoglobin levels (10-12g/dL), regardless of prior erythropoietin stimulating agents (ESAs) received and dialysis status.
FibroGen explained in the press release that the mechanism of action of roxadustat is not the same as ESAs’. Roxadustat is a HIF-PH inhibitor that triggers the body’s natural response to a reduction in the level of oxygen in the blood. “This response involves the regulation of multiple, coordinated processes that lead to the correction of anemia with a reduced need for intravenous iron,” according to the company.
Roxadustat is the second CKD drug in recent weeks to receive a CRL in response to an NDA. Ardelyx announced at the end of July that they had received a CRL from the FDA requesting an additional clinical trial to support approval of tenapanor, the company’s novel treatment for the control of serum phosphorus in adult patients with CKD on dialysis.4
1. Update on US regulatory review of roxadustat in anaemia of chronic kidney disease Published online August 11, 2021. Accessed August 11, 2021. https://bit.ly/2VN1DIj.
2. Status on FDA Advisory Committee vote on roxadustat in anaemia of chronic kidney disease. Published online July 16, 2021. Accessed August 11, 2021. https://bit.ly/3iBLJZS.
3. Astellas Receives Positive CHMP Opinion for EVRENZO™ (roxadustat) for Adult Patients with Symptomatic Anemia of Chronic Kidney Disease. Published online June 25, 2021. Accessed August 11, 2021. https://yhoo.it/3vUerZh.
4. Ardelyx Receives Complete Response Letter from U.S. FDA for New Drug Application for Tenapanor for the Control of Serum Phosphorus in Adult Patients with CKD on Dialysis. Published online July 29, 2021. Accessed August 11, 2021. https://prn.to/3zNth6c.