- The Food and Drug Administration rejected an Akebia Therapeutics' anemia pill vadadustat, the company announced Wednesday, over concerns the drug isn't as safe as currently approved injectable medicines for patients with chronic kidney disease.
- The FDA concluded the data in Akebia's application don't support a "favorable benefit-risk assessment," citing an increased risk of clotting events or drug-induced liver injury, according to the statement. Akebia will have to run more studies if it wants to get the agency's OK. The company plans to request a meeting with the FDA to discuss the details of its decision.
- The rejection marks the second time the regulator has rejected a prospective anemia pill since last August, when the FDA turned back a rival drug from FibroGen for similar reasons. Those rulings raise questions about the U.S. approval prospects of a third medicine from GlaxoSmithKline that recently succeeded in late-stage testing.
Akebia and FibroGen's drugs are part of a group of medicines known as oral hypoxia-inducible factor prolyl hydroxylase, or HIF-PH inhibitors, that have long been billed as convenient and possibly safer alternative to widely used injectable medicines for anemia associated with chronic kidney disease. Those drugs, like Amgen's Epogen and Aranesp, were linked to heart problems resulting from blood clots, prompting the FDA to step in and recommend lower doses.
But HIF-PH blockers, which trick the body into thinking its in a low-oxygen environment, have been unable to fulfill their promise, at least in the eyes of U.S. regulators. For example, the FDA rejected FibroGen's drug after it performed worse than Aranesp on a measure of cardiovascular safety — clinical results the company had to restate because of after-the-fact changes to how the data was analyzed.
Akebia's medicine, vadadustat, also looked less safe than Aranesp in Phase 3 testing. But Akebia chose to submit its data to the FDA nonetheless, believing the totality of its results, which included positive findings from two other large-scale clinical trials, were sufficient. Analysts were generally skeptical of its chances, though some argued the FDA might approve the drug only for patients on dialysis. Instead, the agency has issued a full rejection, instructing Akebia to run new trials to "demonstrate a favorable benefit-risk assessment."
Those rulings cast doubt on the U.S. approval chances for GlaxoSmithKline's drug, though the treatment, daprodustat, was able to raise patients' hemoglobin levels without posing a greater risk of heart problems than Aranesp. GSK has said it plans to seek FDA approval by the end of June.
U.S. regulators have been outliers in their evaluations of anemia pills. For example, FibroGen's drug, roxadustat, is approved in Europe. Akebia's treatment is being reviewed by Europe's drug regulator and both its medicine and GSK's already are on the market in Japan.
Akebia shares fell 67% to $0.80 in afternoon trading.