Easing concerns, FibroGen, AstraZeneca secure FDA date for their anemia drug in broad chronic kidney disease population

Armed with a new chief following the unexpected passing of longtime CEO Thomas Neff last year, FibroGen is off to the races with its controversial AstraZeneca-partnered anemia drug. The FDA has accepted the company?s application to market the oral therapy ? which is positioned to replace the standard of care ? in patients with chronic kidney disease regardless of dialysis status.

The drug, roxadustat, which is designed to stimulate the production of red blood cells by mimicking the effect of high altitude in humans was approved in China last year ? marking perhaps the first instance of a multinational pharmaceutical company AstraZeneca paving the way for the sale of a medicine in China, before the United States or Europe.

FibroGen and AstraZeneca are locked in a race with Akebia, whose experimental drug vadadustat has a similar mechanism of action. But pivotal vadadustat data are not expected until later in 2020. The dominant drugs for anemia in the United States are red-blood-cell boosting erythropoiesis-stimulating agents (ESA) from Amgen. The standard-of-care does, however, come with high cardio risks ? but given the steep overall mortality rate for this patient population, it is a risk regulators consider acceptable.

Healthy kidneys produce a hormone called erythropoietin (EPO), which prompts the bone marrow to make red blood cells that carry oxygen throughout the body. If diseased or damaged, kidneys are unable to make enough EPO, resulting in fewer blood cells, and eventually anemia.

FibroGen, which originally developed the drug, has partnered with AstraZeneca since 2013. On Tuesday, the company ? which brought on Lilly vet Enrique Conterno to take over the reins last month ? said the FDA was expected to make its decision by December 20 ? triggering a $50 million milestone payment from AstraZeneca.

?(R)eassuringly, the FDA simultaneously accepted the NDA filing for both DD (dialysis-dependent) and NDD (non-dialysis dependent) indications, which should partially remove some of the negative overhang on FGEN?s stock associated with lingering skepticism surrounding the prospects for a successful filing and approval in the more controversial NDD indication,? SVB Leerink?s Geoffrey Porges wrote in a note.

?Although a priority review now appears to be off the table, the PDUFA date timeline remains consistent with our expectations for an AdCom to occur sometime in Q3 2020.?

While roxadustat did meet the main goal of enhancing hemoglobin levels in a pair of pivotal studies, the drug has a checkered past.

Last spring, FibroGen came under fire for masking some unsavory safety data indicating the drug could underwhelm in key market segments ? in the top-line messaging of ?positive? pooled safety data on the drug from two sets of results on major cardio events (MACE and MACE+) required by US and European regulators. The messaging inspired a short attack betting that roxadustat would come up short when researchers unveil the hard numbers on the pivotal safety data on major cardio events compared to placebo and EPO.

Then, in November, some concerns were assuaged when AstraZeneca broke out the pooled hazard ratios on roxadustat safety. Investigators assessed the drug against placebo for non-dialysis dependent CKD patients, and against EPO in dialysis patients, including a population of patients new-to-dialysis, or incident dialysis. But even at its worst hazard ratio on the MACE endpoint, researchers showed roxadustat?s safety profile was comparable to EPO ? which dampened the blockbuster expectations that would have come with achieving superiority.

Meanwhile, some critics panned the analysis because the companies looked at the full intent-to-treat population. As placebo patients were switched to EPO, they were more likely to experience CV events, swinging the pendulum in roxadustat?s favor.

?Major debates revolve around whether it?s going to actually be approved and if it?s a broad label in DD and NDD and if they get a black box (we assume yes because FDA is super conservative ? and we think Street understands that?s probable so we like the upside if they do not get a black box),? Jefferies? analyst Michael Yee wrote in a note.

?We think FDA is on board with the statistics and data (per FGEN?s FDA meeting minutes, discussions, and dialog), and partners AZN and Astellas have been positive (vocally) on the results. AZN wouldn?t have helped file and paid a large $50M milestone if they didn?t believe in the drug.?

Rival Akebia?s data is now in focus.

Yee said he expected the company?s drug, vadadustat, to hit the endpoints of on efficacy and ?non-inferiority? on CVOT safety versus EPO, like FibroGen $FGEN. ?But we will look to see if they can hit on ?superiority? to EPO on incident dialysis since this is where FGEN had ?superior? MACE CV data of +30% benefit in a pooled analysis.?

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