While anemia med roxadustat’s U.S. fate remains in limbo, FibroGen partner Astellas is trumpeting data that could help clear the air around its disputed safety profile.
In a pooled analysis of four phase 3 studies, roxadustat proved at least as safe as standard of care erythropoietin therapies when it came to patients’ risk of cardiovascular side effects or death, Astellas said Thursday at the 59th Congress of the European Renal Association (ERA).
Roxadustat’s late 2018 China approval in anemia associated with chronic kidney disease (CKD) made it the first member of the HIF-PH inhibitor class to win a regulatory green light anywhere in the world. The drug once carried blockbuster expectations, but an FDA rejection last summer and an ongoing FibroGen-AZ stalemate over the drug’s future have left roxadustat’s U.S. fate uncertain.
While FibroGen tapped AstraZeneca to lead roxadustat marketing in the U.S., Astellas is already selling the drug in markets such as Europe. There, the med won approval under the brand name Evrenzo last summer.
The latest clutch of roxadustat data should “further validate” the med’s overall safety and efficacy profile as a new oral treatment option for patients with anemia of CKD, Txema Sanz, senior vice president, medical specialties at Astellas, said in a recent interview.
The analysis showed “no evidence of an increased risk of cardiovascular events or mortality” with roxadustat versus standard-of-care erythropoiesis-stimulating agents, Astellas' Sanz pointed out.
Still, safety is the only reason the FDA turned the drug away back in August 2021. Ahead of an advisory committee last year, FDA staffers said the drug's "efficacy is not in question." The "principal issue" was safety, they said.
The FDA's review cited concerning evidence of blood clotting for roxadustat, not just against placebo in non-dialysis patients, but also when pitted against Amgen and Johnson & Johnson’s standard-of-care Epogen/Procrit. FDA reviewers also linked roxa to increased risk of death, serious infections and more versus the standard-of-care meds.
Astellas' Thursday analysis didn't touch on the blood clot issue. But it found that across both nondialysis patients and those just starting dialysis, side effects from treatment “occurred commonly” in both the roxadustat and ESA arms.
Those side effects were “generally comparable” between the roxadustat and erythropoietin therapy arms, including those that prompted a study discontinuation, an Astellas spokesperson further explained over email. The most common side effects were hypertension, end-stage kidney disease, diarrhea and high potassium.
"Across all our studies the incidence of [treatment-emergent adverse events] was comparable to ESA and reflective of the underlying CKD population studied," the company added via email.
Epogen and Procrit's cardiovascular risks are well-documented and are therefore not used much to treat less severe kidney disease patients who aren't on dialysis.
That aligns well with Astellas' own vision for roxadustat. The company figures the drug holds the most promise in moderate-to-severe anemia of CKD patients who’ve not yet started dialysis, as well as dialysis-dependent patients who don’t respond well to ESAs, Sanz said. Doctors, too, have told the company they see the greatest opportunity for roxadustat in the "pre-dialysis" space, just around the time patients are starting to become severely anemic, he added.
Anemia of CKD can take a “significant” toll on patients’ ability to exercise, work and do other daily tasks, Sanz pointed out. Meanwhile, traditional treatment with injectable ESAs and iron infusions is burdensome and time-consuming. Given the meds’ similar-looking safety profiles, the choice between visiting a doctor’s office for multiple injections a month versus a thrice-weekly oral option like roxadustat makes the latter’s convenience edge apparent, he explained.
Despite the roxa dust-up stateside, the med is approved in many other countries and is already making a “very positive” difference in patients’ lives, Sanz added.
Since launch, the drug has charted more than 1.5 million patient months of exposure worldwide, the executive said.
Astellas is partnered with FibroGen on roxadustat’s marketing and development in places like Japan, Europe and the Middle East. Sold as Evrenzo, the drug is also approved in countries like the United Kingdom and China, where FibroGen has teamed up with AstraZeneca.