- The Food and Drug Administration won't approve FibroGen's anemia pill without the company conducting further clinical study on its safety, casting doubt on the medicine's future in the U.S.
- In July, an outside advisory panel to the FDA recommended the agency reject the drug for use in kidney disease patients due to safety concerns. FibroGen had been seeking approval for use in patients who require dialysis as well as in those who do not.
- In a Wednesday statement, FibroGen didn't give details about the FDA's request for more data and said it will “discuss next steps” with partner AstraZeneca. The medicine, roxadustat, is already approved in China, Japan, Chile and South Korea and could be cleared in Europe as soon as this month.
The future of roxadustat in the U.S. hinges on what exactly the FDA is requiring, and whether Fibrogen and AstraZeneca are willing to follow through with additional study.
A new clinical outcomes trial, for instance, would likely be a "non-starter" for the companies because of the costs involved, Annabel Samimy, an analyst at the investment bank Stifel, wrote in an Aug. 11 note to clients. Other options could possibly involve a titration study or collection of data from ongoing trials or international markets.
Before receiving the FDA letter, FibroGen CEO Enrique Conterno told analysts earlier this week that a rejection would result in a "significant reallocation of resources and corresponding reduction in expenses." He didn't give details, saying he didn't want to get ahead of the agency's decision. But cost-cutting appears likely to be on the table for Fibrogen, which has seen its shares tumble in value by two-thirds so far this year.
Roxadustat is part of a new class of medicines that block a protein called hypoxia inducible factor prolyl hydroxylase, or HIF-PH. The drug is designed to work by tricking the body into responding as if it's in a low-oxygen environment and needs to produce red blood cells.
The drugs are designed as oral alternatives to medicines such as Amgen's Epogen, which require an infusion. Researchers had hoped the new drugs would offer safety advantages over older injectable drugs that have been linked to heart attacks and strokes.
While the rejection isn't a surprise after the advisory panel's ruling, it's another setback for FibroGen's pill in the U.S. The biotech stunned investors in April when it disclosed that safety results it touted to support the product weren't accurate because "post hoc changes" made them appear better than under an original analysis plan.
The employees involved in the post hoc changes are no longer at the company, and Conterno told investors this week that he didn't believe the issue affected the FDA advisory panel vote. Committee members instead voiced concern about an analysis of studies in dialysis patients that showed a greater risk of major cardiovascular issues than drugs such as Epogen.
At the time, FibroGen proposed FDA approval of a lower dose and target for hemoglobin, the red blood cell protein that carries oxygen. But panel members said they weren't comfortable recommending a different dosing regimen without more clinical testing.
Some of the experts also raised the possibility that the mechanism of action in the new class — blocking HIF-PH — may be creating a risk for blood clots.
But other companies working on HIF-PH blockers remain confident in the drug class. GlaxoSmithKline last month announced positive Phase 3 data for its daprodustat drug and Akebia claims its experimental vadadustat medicine may now be positioned to grab more of the market as a potentially first-in-class product. The FDA is set to act on Akebia's vadadustat by March 29, 2022.
"We are highly focused on pre-launch activities," Akebia CEO John P. Butler said in an emailed statement. "We remain confident in the clarity and quality of our data."