Phase 3 Trial Shows Positive Efficacy, No Increased Cardiovascular Risk for Hemoglobin-Increasing Drug

Phase 3 Trial Shows Positive Efficacy, No Increased Cardiovascular Risk for Hemoglobin-Increasing Drug

In pooled efficacy and cardiovascular (CV) safety analyses from a phase 3 program, roxadustat for the treatment of patients with anemia from chronic kidney disease (CKD) was shown to have positive efficacy and no increased CV risk.¹

The primary efficacy endpoint was achieved in the analyses for both non-dialysis-dependent patients as well as dialysis-dependent patients. According to a statement from AstraZeneca, these data, combined with other statistical analyses, will be included in the regulatory submission in the United States, which is expected in the fourth quarter of 2019.

Anemia can be a serious adverse effect for patients with CKD, which affects more than 200 million patients globally.¹ Anemia is associated with increased risk of hospitalization, CV complications, and death.¹

According to data from the US Renal Data System, of the 509,000 patients on dialysis in the United States in 2016, approximately 80% were being treated with erythropoiesis-stimulating agents, which stimulates bone marrow to make red blood cells.²

Roxadustat is an oral first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). The drug improves iron regulation and overcomes the negative impact of inflammation on hemoglobin synthesis and red blood cell production by downregulating hepcidin.¹

The global phase 3 program for roxadustat includes more than 9000 patients across 7 studies, 1 of which was no used in the pooled CV safety analyses.¹

In a predefined subgroup of incident dialysis patients, defined as patients who have been on dialysis for 4 months or less, roxadustat reduced the risk of major adverse cardiovascular events (MACE) as well as major adverse CV events plus unstable angina requiring hospitalization or congestive heart failure requiring hospitalization (MACE+).¹ It also showed a trend toward lower risk of all-cause mortality when compared with epoetin alfa.¹

Among patients who were not dependent on dialysis, the risk of MACE, MACE+, and all-cause mortality in roxadustat patients was comparable to the placebo.¹ Among these patients, there averaged a mean increase from baseline in hemoglobin levels over weeks 28 to 52 of 1.85 g/dL in patients receiving roxadustat, compared with 0.13 g/dL in patients receiving the placebo.¹

In dialysis-dependent patients, there was no increased risk of MACE and all-cause mortality in patients receiving roxadustat, and there was a lower risk of MACE+ compared with patients receiving epoetin alfa.¹ Among this population, the analyses found a statistically significant mean increase from baseline of hemoglobin levels averaged over weeks 28 to 52. Patients treated with roxadustat saw increased hemoglobin levels averaging 1.22 g/dL, compared to 0.99 g/dL in patients receiving epoetin alfa.¹

"Roxadustat is the first in a new class of medicines for the treatment of anemia from chronic kidney disease," said Robert Provenzano, MD, associate professor of medicine at Wayne State University, in a statement. "This pooled cardiovascular safety data, together with strong efficacy data, support its potential as an important new treatment option for patients with anemia from chronic kidney disease who have seen little to no innovation in decades."¹

REFERENCES

• United States Renal Data System. 2017 Annual Data Report, Chapter 2: Identification and Care of Patients with CKD. USRDS website. https://www.usrds.org/2017/view/vq_02.aspx. Accessed Nov. 12, 2019.
• Roxadustat Phase III programme pooled analyses showed positive efficacy and no increased cardiovascular risk in patients with anaemia from chronic kidney disease [news release]. Cambridge, UK; Nov. 8, 2019. AstraZeneca. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/roxadustat-phase-iii-programme-pooled-analyses-showed-positive-efficacy-and-no-increased-cv-risk-in-patients-with-anaemia-from-chronic-kidney-disease.html. Accessed Nov. 12, 2019.