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Pooled efficacy and cardiovascular (CV) analyses of roxadustat in the treatment of anemia in CKD patients on and not on dialysis
Session: High-Impact Clinical Trials
Presenter: Robert Provenzano, MD, FACP, FASN, Chief Medical Officer, Nephrology Practice Solutions & Vice President, Medical Affairs
Before a packed crowd, Robert Provenzano, MD, FASM, DaVita Healthcare, presented pooled efficacy and cardiovascular (CV) safety analyses from the pivotal Phase III program assessing roxadustat for the treatment of patients with anemia from chronic kidney disease (CKD).
“Here’s what every clinical nephrologist knows: All dialysis patients aren’t created equal. There’s CKD 1, 2, 3, 4, 5. There are different physiological requirements. There’s the non-dialysis dependent CKD pool, dialysis dependent CKD pool, and going deeper, the incident dialysis pool. They’re all different populations. And our studies pool our knowledge on treating anemia in each of them.”
The results, as Dr. Provenzano explained, focus on primary efficacy end points and cardiovascular safety endpoints — with roxadustat demonstrating efficacy in both end points.
While the results represent an important advancement, Dr. Provenzano added that it’s about time. “We’ve been treating anemia for 25 years, and standards are a lot different today. When you look at the trials that preceded this trial, we learned a lot about managing hemoglobin and outcomes. When you look at the roxadustat trial, it’s everybody — and you can see disproportionately how many patients were severely anemic and had severe chronic kidney disease.”
That leads directly to the importance of the Phase III program assessing roxadustat for the treatment of patients with anemia from CKD. “Many of you are here today because we now know that the drug is effective in the cohorts of patients that we treat everyday,” Dr. Provenzano said.
The doctor led with a review of roxadustat’s efficacy. Put simply, roxadustat’s efficacy was demonstrated. Here’s how:
- The drug achieved primary efficacy endpoint (change in Hb) in individual studies and pooled analyses.
- With non-dialysis dependent CKD patients, roxadustat was superior to a placebo and efficacious regardless of iron-repletion.
- With dialysis dependent CKD patients, roxadustat achieved a higher mean Hb increase than epoetin alfa, particularly in inflamed patients. In addition, less IV iron was required in roxadustat arm than in epoetin alfa.
- The drug resulted in a lower requirement for blood transfusion.
- In the non-dialysis dependent CKD group, roxadustat patients compared with placebo patients.
- In dialysis dependent CKD patients, roxadustat patients compared with epoetin alfa patients.
- The drug presented additional benefits for non-dialysis dependent patients.
- There was reduced LDL cholesterol.
- There was less decline in eGFR.
Roxadustat further demonstrated cardiovascular safety in all study populations.
- In the non-dialysis dependent group, risk of MACE (major adverse cardiovascular event), MACE+ (MACE plus unstable angina requiring hospitalization and congestive heart failure during hospitalization), and all-cause mortality in roxadustat patients were comparable to placebo in non-dialysis dependent patients
- As per incident dialysis, roxadustat patients had 30 percent lower risk of MACE, a 34 percent lower risk of MACE+ then epoetin alfa, and a trend towards lower all-cause mortality relative to epoetin alfa.
- In the dialysis-dependent group:
- Roxadustat patients had a lower risk of MACE+ than epoetin alfa patients.
- Risk of MACE and all-cause mortality in roxadustat patients were not increased compared to epoetin alfa in dialysis-dependent patients.