After an FDA cold shoulder, FibroGen and partner AstraZeneca still aim to pave a way to market for anemia therapy roxadustat—even if it means conducting another clinical trial. The two companies are now betting the drug’s U.S. future on an upcoming meeting with the FDA.
FibroGen and AZ have scheduled a meeting with the FDA to discuss a potential path forward for roxadustat in anemia of chronic kidney disease, FibroGen CEO Enrique Conterno told investors on a conference call Tuesday.
“The question is really, how can we ensure that we can conduct a trial that meets the complete response letter for us to be able to have commercial access in the U.S. in anemia of CKD,” Conterno said. The company aims to run the trial “in an expeditious manner,” he added.
As the partners navigate that process, FibroGen has started cutting expenses to focus on roxadustat and pancreatic cancer candidate pamrevlumab. The California biotech plans to reduce its projected spending by about $100 million a year for the next three years, Conterno said. It will also remove about 100 U.S. positions, of which 30% are existing jobs.
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In August, the FDA turned down roxadustat’s application in anemia for kidney disease patients following negative opinions from an external advisory committee and a rough FDA internal review. Previously, industry watchers thought roxa could become the first drug in the oral HIF-PHI class to reach the U.S. market. Analysts had pegged blockbuster expectations to roxa based on the notion that it could offer safety benefits over traditional erythropoietin therapies.
But the agency rejected roxa in both dialysis- and nondialysis-dependent patients after linking it with an increased risk of blood clots, serious infections, seizures and other metabolic and gastrointestinal side effects. Given the obvious defeat from roxa’s existing trials, a separate study seems inevitable if FibroGen and AZ still intend to pursue an FDA approval.
The most concerning safety signal flagged by the FDA centers on roxa’s heart safety profile, including an elevated risk of a composite marker of major adverse cardiovascular events. Both the FDA and FibroGen have hypothesized that the problem might stem from a fast hemoglobin overshoot seen with roxa. But as experts on the advisory committee pointed out in rejecting FibroGen’s proposal of a different dosing strategy, it’s only a theory without a clinical trial to back it up.
“That's something we're clearly going to explore with the FDA,” Mark Eisner, FibroGen’s chief medical officer, said of the dose adjustment plan during this week's call. FibroGen still intends to eventually get a label that covers both dialysis and nondialysis patients, he added.
Roxa has scored approvals in China, Japan and most recently Europe as Evrenzo. In the third quarter, roxa sales in China reached $57.8 million, FibroGen said.
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After the FDA rebuff, analysts speculated that AZ might walk away from the partnership. But CEO Conterno said the AZ relationship is “healthy” as the two try to “have an aligned path forward.”
Whether AZ will keep its toe in roxa is likely dependent on the outcome of the FDA meeting, SVB Leerink analyst Geoffrey Porges wrote in a Wednesday note to investors. The size, duration and cost of the required trial or trials, the potential breadth of the drug's label and the estimated timing of an approval relative to competitors are possible determinants, Porges added.
GlaxoSmithKline’s daprodustat, approved in Japan under the brand Duvroq, seems to have the best profile in the HIF-PHI class. Detailed data unveiled last week showed that the GSK med matched up to erythropoiesis-stimulating agents in terms of heart safety in both dialysis and nondialysis patients. By contrast, Akebia Therapeutics’ vadadustat missed its MACE goal in the nondialysis population.