The results of phase 3 studies of roxadustat, a drug in the new class of hypoxia-inducible factor stabilizers, are satisfying in terms of both efficacy and safety, said Jay Wish, MD, professor of clinical medicine at Indiana University and chief medical officer for dialysis at Indiana University Health.
The results of phase 3 studies of roxadustat, a drug in the new class of hypoxia-inducible factor (HIF) stabilizers, are satisfying in terms of both efficacy and safety, said Jay Wish, MD, professor of clinical medicine at Indiana University and chief medical officer for dialysis at Indiana University Health.
What are the implications of the newly released roxadustat data?
Well, the data that were just presented yesterday and today [November 7 and 8] represent the phase 3 studies of roxadustat, which is one of this class of HIF stabilizers. It’s the first to market in over 9000 patients worldwide. And there are basically 3 populations of patients that were studied. There were nondialysis patients with chronic kidney disease. There were incident dialysis patients, most of whom had not previously required or not previously been treated with ESAs [erythropoiesis-stimulating agents], and then were randomized to either an ESA or roxadustat. And then there were prevalent dialysis patients that were converted from an ESA to either roxadustat or continued on ESA, and the pooled data as well as the individual populations were presented today [November 8].
The results were very, very satisfying. The roxadustat demonstrated superiority to placebo, which is the comparator, in the nondialysis population, both in terms of efficacy and comparable safety. So there were no safety signals compared to placebo in the nondialysis population, which had placebo as the comparator. And for those of us who are concerned about the MACE [major adverse cardiovascular end point] outcomes that have been described with the ESAs, noninferiority to placebo is pretty much as good as you can get in terms of safety. So this is very reassuring for us who were concerned that the class of HIF stabilizers and perhaps roxadustat, the first one that has completed its long-term trials, might also have similar safety signals like with MACE, major adverse cardiovascular end points, but that did not seem to be the case when compared to placebo.
In the dialysis patients, both the incident and the prevalent, the comparator was ESAs, and what we found was that there was comparable efficacy—actually, it’s a little superior efficacy—to ESAs in those populations, and there was improved safety, that in the incident dialysis population in particular, there was a lower incidence of MACE and MACE-plus outcomes, MACE outcomes plus hospitalization for heart failure and unstable angina, in the incident dialysis patients.
Now that was not seen in the entire dialysis sample, but since this was basically an event-based outcome, you’re going to have a more vulnerable population, meaning the incident dialysis patients having more events, and that’s probably why they were able to detect the difference in events and a superiority in safety in the incident dialysis patients that was not detected in the prevalent dialysis patients: because in the prevalent dialysis patients, the event rate was just much lower.