Amid dispute with FDA, Akebia proposes new dosing for oral anemia drug in kidney disease

Akebia Therapeutics isn’t giving up on its oral anemia drug vadadustat despite an FDA rejection and a partnership gone awry. Now, just as the company challenges the FDA decision, Akebia has offered top-line data for a reduced dosing regimen.

Vadadustat, given three times a week, matched up to Roche and CSL Vifor's erythropoiesis-stimulating agent (ESA) Mircera at controlling hemoglobin levels in dialysis patients with anemia that’s caused by chronic kidney disease.

Akebia unveiled the phase 3 win from the FO2CUS trial on Monday. Vadadustat was non-inferior to Mircera at two different dosing levels when measured during two evaluation periods, according to the company.

Vadadustat is currently available in Japan as a once-daily med for treating chronic kidney disease-related anemia. Akebia’s local partner, Mitsubishi Tanabe Pharma, scored that approval in 2020 and has been selling it under the brand name Vafseo. The European Commission is also expected to hand out a green light in dialysis-dependent patients soon following a backing from drug reviewers at the European Medicines Agency.

In the clinical trials supporting those applications, vadadustat was tested as a daily drug, and its doses could be adjusted to a maximum of 600mg.

With the FO2CUS study, Akebia is proposing two dosing strengths—600mg and 900mg—given three times a week.

The reduced dosing frequency is important because it matches patients’ dialysis visits and “has the potential, if approved, to provide an oral alternative to the standard of care," Akebia’s R&D chief Steven Burke said in a statement Monday.

During a follow-up of the primary endpoint between weeks 20 and 26, dialysis patients who took 600mg vadadustat saw their hemoglobin levels drop an average 0.43g/dL. And the 900mg group experienced an average decrease of 0.23g/dL.

Akebia didn’t disclose the control group’s performance, only saying that the difference between vadadustat and Mircera came within a prespecified noninferiority margin of 0.75g/dL.

The positive readout comes as Akebia fights with the FDA over a complete response letter the agency handed out to vadadustat in March 2022. At the time, the FDA raised safety concerns around the drug’s cardiovascular risks and liver injuries.

For its part, Akebia believes vadadustat’s benefit-risk portfolio looks positive at least in dialysis-dependent patients, who have more severe kidney disease than those not on dialysis. The company in October filed a formal complaint to dispute the FDA’s decision in the dialysis group.

In an update last week, Akebia said it had a “productive discussion” with Peter Stein, M.D., director of the FDA’s Office of New Drugs, who is presiding over the dispute. Stein is consulting with experts within the agency in a process that could be finished by June, and he expects to give Akebia a response to the appeal within thirty days after that, the company said.

The dispute only concerns the company’s original application, so the new data from FO2CUS won’t be considered, an Akebia spokesperson told Fierce Pharma. Akebia didn’t offer detailed cardiovascular or liver safety analyses for the new study in its Monday release but said the top-line results indicate that the safety profiles were comparable between treatments.

In FO2CUS, 44.5% of all vadadustat patients experienced serious treatment-emergent side effects, compared with 44.7% in the Mircera group, the company said.

Meanwhile, thanks to the FDA rejection, Otsuka recently backed out of its U.S. and EU collaboration with Akebia on vadadustat. If the FDA eventually reverses its decision and approve vadadustat in dialysis patients, Akebia plans to market it under an existing deal with CSL Vifor.

In Europe, Akebia is in the process of securing a partner, the company spokesperson said. After an expected approval there, Akebia expects that partner will talk to the EMA about a potential label expansion to include the three-times-a-week regimen, the spokesperson added.

Vadadustat belongs to an emerging class of drugs known as HIF-PHI. The class once bore high hopes as potentially convenient alternatives to ESAs, but cardiovascular safety became a major concern at the FDA. As Akebia fights for an approval, GSK in February snatched the first FDA nod for the class with Jesduvroq in dialysis patients only.