VIDEO: Expert discusses impact of vadadustat data for non-dialysis CKD
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Vadadustat did not meet the primary safety endpoint of the PRO2TECT program for the treatment of anemia in patients with non-dialysis-dependent chronic kidney disease, according to data presented at ASN Kidney Week.
The primary safety endpoint was non-inferior vs. darbepoetin alfa in time to first occurrence of major adverse cardiovascular events (MACE), which is the composite of all-cause mortality, non-fatal myocardial infarction and non-fatal stroke. Jay B. Wish, MD, professor of clinical medicine at Indiana University School of Medicine and co-chair of the Nephrology News & Issues Editorial Advisory Board, discussed the data and its impact in a video interview.
“Not surprisingly, the efficacy was pretty much the same when you compared vadadustat to ESA, both in the untreated patients and the patients who had previously been on ESA. The treatment-related adverse events were pretty much the same in the two groups,” Wish said. “So, really, the issue is this one particular safety signal – MACE.”
Although the only inferior primary outcome considered was MACE, Wish said that is the one the FDA is going to consider when they adjudicate the new drug application for vadadustat.
“So, this is clearly of concern, not only because it suggests that this drug may be less safe than ESA, but also what is its likelihood of being prescribed? The other question is: is the FDA going to approve it at all?” he said.
Wish noted that these data should be put into context of the dialysis-dependent CKD data, where vadadustat showed similar efficacy and noninferior safety to darbepoetin alfa.
“That’s pretty much a slam-dunk in terms of FDA approval, but if you’ve got a drug in the non-dialysis setting that is less safe than ESA, even if it is as efficacious, then that jeopardizes the FDA approval for the non-dialysis indication, or could even jeopardize the approval or make the safety warning for the dialysis population perhaps even more restrictive.”
Wish also speculated on how the FDA is going to interpret these data. Whether the safety signal on vadadustat in the non-dialysis will affect the FDA adjudication of the new drug application for roxadustat, another HIF stabilizer up for approval, is still unknown, he said.
“The roxadustat data would be able to stand on its own and not be tainted by the vadadustat data because this shows us that these are not all equivalent drugs. Vadadustat has a different pharmacokinetic profile than roxadustat and that may be the key to the difference in the safety effects,” Wish said.
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Chertow GM, et al. #FR-OR54. Presented at: ASN Kidney Week. Oct. 22-25 (virtual meeting).
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