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Vafseo is currently only approved in dialysis patients with chronic kidney disease-related anemia thanks to safety concerns raised by the FDA. Despite finally winning a hard-fought FDA approval for its chronic kidney disease (CKD) anemia drug Vafseo last year, Akebia Therapeutics’ endgame remains focused on pushing the therapy into a wider pool of patients both on and off dialysis.Now, in tandem with Vafseo’s U.S. market debut, Akebia is putting its CKD expansion plans into action.Akebia on Thursday laid out plans to kick off a phase 3 clinical trial, dubbed Valor, to assess Vafseo as a potential treatment for anemia in late-stage CKD patients who aren’t on dialysis.Vafseo, which is part of the hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI) branch of meds, was approved last March to treat CKD-associated anemia in patients who have received dialysis for at least three months.Vafseo already boasts CKD anemia approvals in both dialysis and nondialysis patients in some countries outside the U.S., but safety concerns raised by the FDA—mainly around cardiovascular risks—led to the drug receiving a more limited label in the U.S.Regarding Valor, Akebia aims to recruit roughly 1,500 U.S. patients with stage 4 or 5 CKD not on dialysis for the late-stage cardiovascular outcomes trial, according to a presentation at the J.P. Morgan Healthcare Conference in January.The company said Thursday in its 2024 annual report that it has now submitted a trial protocol to the FDA and expects to meet with the regulator to discuss its designs. If all goes to plan, Akebia hopes to start the study in the second half of 2025.As for the population Akebia is targeting, stage 4 CKD is severe and points to advanced kidney damage with a high risk to progress to kidney failure. Stage 5 of the disease describes the point at which a patient’s kidneys fail, leading to dangerous buildups up fluid, electrolytes and waste in the body.Patients with end-stage CKD need dialysis or a kidney transplant to continue living, though some choose to manage their symptoms with conservative care instead.Akebia estimates there are around 550,000 patients with stage 4 or 5 CKD who are anemic and not receiving dialysis, though the company asserts that just 25% of those patients are currently treated for anemia. The company noted in its annual report that there are well-known risks to beginning dialysis with unmanaged anemia, while use of erythropoietin stimulating agents (ESAs)—a common class of CKD anemia drug—is “low and declining in the non-dialysis patient population.”“We believe the availability of an oral HIF-PH inhibitor within the non-dialysis patient population could address the issues contributing to the decline in ESA use among that patient population,” the company said in its annual filing.Akebia additionally pointed to a recent Spherix Global Insights report that found 78% of doctors said they would increase anemia treatment for nondialysis CKD patients if an HIF-PH inhibitor were approved.  A U.S. approval bid in nondialysis patients has long been part of Akebia’s overall plan for Vafseo, with the company noting at JPM that its upcoming Valor study could unlock a "multi-billion-dollar U.S. market opportunity."Meanwhile, when the company set Vafseo’s price tag notably higher than that of GSK’s rival HIF-PHI drug Jesduvroq in July, Akebia’s CEO, John Butler, explained that the company had to account for a potential label expansion under the Inflation Reduction Act (IRA), which limits how quickly drugmakers can raise a medication’s price.“[With] the IRA now, you really can’t change your price when you get a new indication,” Butler said on an investor call last summer. “You have one opportunity to price your drug, so we really have to think about that, that expanded label, as we thought about the strategic pricing and getting outside of dialysis.”Vafseo’s path to the FDA finish line, even in the more limited dialysis patient population, was anything but easy.Akebia’s original approval bid for Vafseo in both dialysis-dependent and nondialysis patients was shot down by the FDA in March 2022, with the regulator flagging safety concerns for the drug, including higher risk of thromboembolic events and liver injury.Akebia contested those concerns and soldiered on, working through a cost-cutting initiative and layoffs as it followed an FDA dispute resolution process that finally bore fruit in May 2023, Butler told Fierce Pharma around the time of the drug’s U.S. approval.Vafseo ultimately crossed the FDA finish line last March, thanks to a resubmission to the FDA girded with additional postmarketing safety data from Japanese patients.Vafseo started shipping out to U.S. patients Jan. 9 and is expected to reel in sales of $10 million to $11 million during its first quarter on the U.S. market, Akebia said in an earnings announcement Thursday.Three of the nation’s top four dialysis organizations have placed orders for Akebia’s anemia drug, and, as of the end of February, more than 500 prescribers had written Vafseo prescriptions, the company added. Akebia delivered the Vafseo progress report as it posted $46.5 million in total fourth-quarter revenue for 2024, down from the $56.2 million haul it brought home for the period in 2023. For the entire year, Akebia generated 2024 revenue of $160.2 million, down roughly 19% compared to 2023.Most of that sum came from Akebia’s phosphate binder Auryxia, which is cleared to control serum phosphorus levels in dialysis patients and as an iron replacement for treatment of iron deficiency anemia in adult CKD patients not on dialysis. The company also generated a small sum from license agreements and collaborations.