OM-8980(Vifor Pharma AG)

After a rocky two years following the FDA's initial rejection of Vafseo, Akebia can finally treat a portion of U.S. patients with anemia from chronic kidney disease. Akebia never lost confidence in its oral chronic kidney disease (CKD) anemia drug Vafseo, even after the FDA nixed its first approval bid two years ago with a complete response letter. Now, the company finally can celebrate a long-awaited U.S. approval. The FDA on Wednesday cleared Vafseo for patients with CKD-associated anemia who have been receiving dialysis for at least three months, kicking off a market showdown between Akebia and GSK. Thanks to a resubmission that included additional safety data from patients in Japan, where the drug has been marketed since 2020, the agency reconsidered its prior concern about potential liver toxicity. For the past two years, Akebia has been doing “everything we have to do” as a company to survive, CEO John Butler said in a recent interview with Fierce Pharma. That included laying off about half its staff and focusing on its lone commercial asset, CKD med Auryxia. The long road to approval The story of Vafseo, from Butler’s perspective, goes something like this: The FDA took issue with the potential for drug-induced liver injury, which Akebia disputed. In fact, the company felt so strongly that the agency made the wrong call that it initiated a formal dispute resolution process. Besides trial results, Akebia was armed with real-world data from Japan, where Mitsubishi Tanabe Pharma is handling commercialization of Vafseo. Japan specifically conducts “outstanding” post-marketing surveillance on its approved meds and hasn’t found any severe instances of drug-induced liver injury, bolstering the drugmaker’s confidence in its safety profile, according to Butler. Vafseo offers a different way to manage anemia than traditional erythropoiesis-stimulating agents, Butler explained. The drug, a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI), works through a unique technique of basically fooling the body into believing it's at a high altitude, effectively encouraging the bone marrow to produce more red blood cells. Vafseo would have been a first-in-class therapy if not for the two-year delay. Instead, that title went to GSK and its Jesduvroq, which was approved in February 2023. The rival also launched strictly in the dialysis-dependent patient population, much to GSK’s disappointment.   In July, GSK revealed its decision to not commercialize the med in Europe, despite winning support from the region’s drug evaluation committee the previous month. The company snatched back its application in Europe and opted to not seek approval in other countries based on the shrunken market opportunity that came without the non-dialysis population. Still, Jesduvroq’s presence in the U.S. market requires Akebia to adapt its original launch strategy, Butler acknowledged. A turnaround from hard times  The FDA nod promises to be “transformational" for the company, the CEO said. After two years of scraping by, Akebia can finally dip its toes in the sizable market for CKD anemia. However, unlike the drug's broad label in Japan, Akebia won't be able to reach the non-dialysis population—at least for now.  Beyond Vafseo, Akebia also looks to build on its pipeline, which already includes two preclinical compounds for acute kidney injury and blindness in newborn babies, or retinopathy of prematurity. All of that work will be done with a markedly smaller workforce than Akebia once had. Shortly after the original FDA rejection, the company had to cut about $60 million to $65 million in annual costs by letting go of 200 staffers, or 42% of its prior headcount. Following the job cuts, the FDA dispute resolution process began in October of 2022 and finally resulted in “a path forward” last May. “You know, you build culture for the hard times, and these were hard times, but people persevered and the light is very bright at the end of the tunnel,” Butler said. Since 2017, CSL Vifor has held the U.S. license to sell the med to Fresenius Medical Care dialysis centers nationwide. That $50 million deal was expanded in 2022 shortly before the FDA’s first decision, allowing Vifor to market Vafseo to “certain third-party dialysis organizations" responsible for treating 60% of U.S. dialysis patients. Akebia looks to launch Vafseo with the intention to “become a new oral standard of care” for dialysis patients, the company noted in its press release. Today, most patients are currently treated with standard injectable erythropoiesis-stimulating agents. With the U.S. nod, the med is now approved in 37 countries. 

Pictured: FDA signage at its office in Washington, DC/iStock, JHVEPhoto The FDA on Wednesday approved Akebia Therapeutics’ oral drug vadadustat, now to carry the brand name Vafseo, for the treatment of adults with anemia due to chronic kidney disease. Vafseo, which is approved for use in 37 countries, is given once daily and is indicated for chronic kidney disease (CKD) patients who have been undergoing dialysis for at least three months. The drug comes with a boxed warning for a heightened risk of death, myocardial infarction, stroke, venous thromboembolism and thrombosis of vascular access. Akebia CEO John Butler in a statement said that Vafseo’s approval will provide “an alternative treatment option for the hundreds of thousands of Americans on dialysis who are diagnosed with anemia due to CKD.” For Vafseo’s launch, the biotech will work with its U.S. commercial team and leverage its partnership with CSL Vifor, which has the exclusive license to market Vafseo to dialysis centers across the country. According to its announcement, Akebia will “execute a launch strategy” for Vafseo with the goal of making the drug the “new oral standard of care” in this patient population. Vafseo is an orally available inhibitor of the hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzyme, which is a central part of the cells’ response to low oxygen levels. This mechanism allows Vafseo to trigger the body’s physiologic response to hypoxia and stimulates the production of erythropoietin to manage anemia. Akebia tested this mode of action in the INNO2VATE program. A New England Journal of Medicine publication in April 2021 showed that Vafseo was not significantly worse than darbepoetin alfa in terms of the change in mean hemoglobin levels. Akebia’s drug also had a similar safety and tolerability pro darbepoetin alfa, primarily measured as the first occurrence of a major adverse cardiovascular event. In addition to INNO2VATE results, the FDA’s approval was also backed by post-marketing safety data from Japan, where Vafseo hit the shelves in August 2020. Wednesday’s FDA nod is the culmination of Vafseo’s long and rough regulatory journey. Akebia first filed for approval in March 2021 but was met with the agency’s rejection in March 2022. In its Complete Response Letter, the FDA cited safety issues with Vafseo and said that the company could run new studies to better demonstrate a positive benefit-risk pro the drug. In November 2022, Akebia filed a Formal Dispute Resolution Request, insisting that Vafseo had a “favorable balance” of benefits and risks, Butler said in an investor call at the time. The regulator in February 2023 ultimately deferred the decision to the Office of New Drugs. In May 2023, the FDA decided that Akebia could resubmit its drug application without needing to perform additional studies. Instead, the biotech could use post-approval safety data from Japan, as well as an updated proposed label that reflects potential risks of heart- and liver-related side effects. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.