FDA Delays Decision on Roxadustat Again, Calls for Advisory Committee Meeting

Compiled by Fan Dongdong

This Monday, AstraZeneca and FibroGen announced that the FDA will convene an Advisory Committee (AdComm) to review the efficacy of roxadustat in treating anemia in patients with chronic kidney disease (CKD), both those requiring dialysis and those not requiring dialysis. Previously, the FDA’s decision date for the review of roxadustat had been postponed from last December to March 20 this year. However, as the FDA has yet to determine a specific date for the meeting, analysts believe that the review of roxadustat may face further delays in the future.

AstraZeneca entered into a collaboration with FibroGen in 2013 for the development and commercialization of the drug, involving an upfront payment of $350 million and milestone payments totaling up to $465 million. Last February, FibroGen announced that the U.S. FDA had accepted the New Drug Application (NDA) for roxadustat, prompting AstraZeneca to make a $50 million payment to FibroGen. AstraZeneca and FibroGen had been hoping that their blockbuster anemia drug, roxadustat, would gain approval in the U.S. market in 2020, but the delay in the review date dashed both companies’ expectations.

If approved, roxadustat could become the first oral HIF-PH inhibitor to receive U.S. regulatory approval. Upon successful market launch, the drug would challenge current standard injectable erythropoietin therapies (such as Amgen’s and Johnson & Johnson’s Epogen/Procrit), with sales potential expected to reach blockbuster status. Geoffrey Porges, an analyst at SVB Leerink, estimated that roxadustat’s revenue could reach $3 billion to $3.5 billion by 2025. However, due to uncertainties surrounding the Advisory Committee meeting, the expected revenue for roxadustat has been adjusted downward to $719 million on a risk-adjusted basis.

As the first HIF-PHI globally, roxadustat promotes the production of endogenous erythropoietin, improves iron absorption and utilization, reduces hepcidin levels, and effectively stimulates erythropoiesis without being adversely affected by inflammation on hemoglobin and red blood cell production. Roxadustat has been proven to induce erythropoiesis. In multiple subgroups of patients with chronic kidney disease, roxadustat can maintain erythropoietin levels at or near the normal physiological range, thereby increasing red blood cell count. It is not influenced by inflammatory status and also avoids the need for intravenous iron supplementation.

There have been concerns about the cardiac safety of roxadustat, particularly in non-dialysis-dependent patients; however, these concerns have been largely alleviated by the pooled analysis results of cardiac-related events from clinical trials conducted by FibroGen and AstraZeneca. Nevertheless, a citizen petition submitted last November requested that the FDA require additional cardiovascular safety data before approving roxadustat.

Mizuho analyst Yang Difei predicted in a report on Tuesday that roxadustat would be approved for two patient groups, but likely with a black box warning. Yang expects the FDA’s advisory committee meeting to take place around June or July this year, with the final review decision on roxadustat delayed until the third quarter and its official market launch postponed to the fourth quarter of 2021.

Notably, roxadustat has been approved in China for the treatment of renal anemia in both non-dialysis and dialysis-dependent patients. Sales of roxadustat reached $29.2 million in the fourth quarter of 2020, up from $22.7 million in the third quarter. In Japan, FibroGen partnered with the Japanese pharmaceutical company Astellas Pharma, and the drug is currently marketed under the brand name Evrenzo.

Reference Source:

1.FDA slaps AstraZeneca, Fibrogen with last-minute roxadustat AdCom, cuing another delay for anemia drug

2.FDA to review AstraZeneca and FibroGen's Roxadustat