AstraZeneca, FibroGen can't agree on roxadustat's path forward in chronic kidney disease after FDA rejection

In the months since the FDA's high-profile rejection for oral anemia drug roxadustat, AstraZeneca and FibroGen have been working to chart a potential path forward for the med in chronic kidney disease (CKD). But the two partners are now split on what that path might look like, leaving dim prospects for a refiling.

Despite “significant discussions,” AstraZeneca and FibroGen “have not been able to find a path forward for AstraZeneca to fund further roxadustat development of anemia of CKD in the U.S.,” FibroGen CEO Enrique Conterno told investors during a conference call Monday.

As a result, FibroGen “does not expect to receive most or all of the remaining” milestones from AstraZeneca related to roxadusat in the U.S. and certain ex-China markets, FibroGen said in its quarterly filing (PDF). As of March, FibroGen had received $439 million from AstraZeneca under that part of the pact.

Because AstraZeneca holds exclusive rights in the U.S., FibroGen can’t bypass the British pharma, Conterno said.  

“We do think there is a path forward in terms of what is the clinical trial that will be required, but we clearly need to be able to agree with this plan with AstraZeneca and funded in order to move forward,” Conterno said.

Alongside its rejection, the FDA has requested additional clinical research for roxadustat as a condition for a potential nod in CKD anemia. The design of the trial—or trials—has been a key focus among industry watchers seeking to evaluate roxadustat’s timeline and market potential. But some Wall Street analysts have noted that AstraZeneca might not be willing to fund another large phase 3 trial, especially as a rival draws nearer to the market.

Once hailed as a blockbuster candidate, roxa last summer hit an FDA wall in both dialysis-dependent and nondialysis CKD patients because of heart-related side effects. AstraZeneca and FibroGen suggested that the cardiovascular safety signals seen in roxa’s clinical trials could be solved by titrating dosing, but the FDA wants proof from a clinical trial.

Roxadustat belongs to a new class of oral medicines called HIF-PH inhibitors. With a Chinese go-ahead for CKD anemia patients on dialysis in late 2018, roxadustat became the first HIF-PHI to be approved anywhere. At the time, the med looked set to become the first drug in its class to reach the U.S., as well.

After roxa's rejection, the FDA in March also snubbed Akebia Therapeutics and Otsuka’s second-in-line HIF-PHI vadadustat in CKD anemia, citing higher risks of thromboembolic events and liver injury. The two setbacks leave GlaxoSmithKline’s daprodustat in a position to potentially become a first-in-class entrant in the U.S., with its FDA decision expected by Feb. 1, 2023.

AZ and FibroGen, meanwhile, have set up a joint venture in China to take care of roxa’s distribution, under which the British pharma giant chips in on sales and marketing. In the first quarter, the drug reeled in $43.5 million sales in the country, flat over the same period last year because a 70% increase in volume offset a price reduction for national reimbursement.

The drug is also sold in the EU and Japan under the same brand name—Evrenzo—through a partnership with Astellas. In Europe, the Japanese pharma has launched in Germany, the U.K., the Netherlands, Austria and the Nordic countries, Conterno said on the call.

Although the U.S. CKD anemia indication appears to have hit a dead end, Conterno said AstraZeneca is still involved in roxa’s development in the U.S. for anemia of myelodysplastic syndromes. Top-line phase 3 data for that program are expected in the first half of 2023.

Meanwhile, FibroGen’s problematic disclosure of roxa’s heart safety data has triggered several investor lawsuits accusing the company and its executives of providing false and misleading information. The U.S. Securities and Exchange Commission has also opened an investigation and has requested documents related to the data.