Roxadustat Phase III Program Pooled Analyses Showed Positive Efficacy and No Increased Cardiovascular Risk in Patients with Anemia from Chronic Kidney Disease Versus Comparators

In non dialysis-dependent patients receiving roxadustat, the risk of MACE, MACE+ and all-cause mortality was comparable to placebo

Dialysis-dependent patients receiving roxadustat had a lower risk of MACE+ and no increased risk of MACE or all-cause mortality versus epoetin alfa

In incident dialysis patients, roxadustat had a lower risk of MACE and MACE+ and showed a trend towards lower risk of all-cause mortality relative to epoetin alfa

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca and FibroGen Inc. (FibroGen) today 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).

The pooled CV safety analyses showed that roxadustat, an oral investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), did not increase the risk of MACE, MACE+ and all-cause mortality in non dialysis-dependent (NDD) compared to placebo and dialysis-dependent (DD) patients compared to epoetin alfa, a current medicine used to treat anemia.

In a clinically important predefined subgroup of incident dialysis (ID) patients, defined as patients who have been on dialysis for four months or less, roxadustat reduced the risk of MACE and MACE+ and showed a trend towards lower risk of all-cause mortality relative to epoetin alfa.

Key safety endpoints consisted of time to major adverse CV events (MACE), defined as all-cause mortality, stroke and myocardial infarction, and time to MACE+, defined as MACE, unstable angina requiring hospitalization and congestive heart failure requiring hospitalization.

The results were presented in an oral late-breaking abstract session at the American Society of Nephrology (ASN) Kidney Week 2019 in Washington, D.C.

Mene Pangalos, Executive Vice President, BioPharmaceuticals, R&D, said: “These highly anticipated results reinforce our confidence in the potential of roxadustat to address significant unmet medical needs among patients with anemia from chronic kidney disease, particularly for those who have recently started dialysis. The pooled analyses showed incident dialysis patients receiving roxadustat had a lower risk of cardiovascular events which is important as these patients may experience higher rates of morbidity and mortality than those on stable dialysis.”

Robert Provenzano, MD, Associate Professor of Medicine, Wayne State University, Detroit, Michigan, US and a primary investigator on the global Phase III program, said: “In the US, roxadustat has the potential to be the first in a new class of medicines for the treatment of anemia from chronic kidney disease. 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.”

Key headline data from the roxadustat Phase III program pooled CV safety analyses

 

Population

Comparator

 

MACE

 

MACE+

 

All-cause

mortality

 

Conclusion

NDD

(n=4,270)

 

Placebo

HR 1.08

(95% CI,

0.94, 1.24)

 

HR 1.04

(95% CI,

0.91, 1.18)

 

HR 1.06

(95% CI,

0.91, 1.23)

 

The risk of MACE, MACE+ and all-cause mortality in roxadustat patients was comparable to placebo

IDi,ii

(n=1,526)

 

Epoetin alfa

HR 0.70

(95% CI,

0.51, 0.96)

 

HR 0.66

(95% CI,

0.50, 0.89)

 

HR 0.76

(95% CI,

0.52, 1.11)

 

In ID patients, those taking roxadustat had a 30% lower risk of MACE and 34% lower risk of MACE+ compared to those taking epoetin alfa, with a trend towards lower all-cause mortality for roxadustat relative to epoetin alfa

DD

(n=3,880)

 

Epoetin alfa

HR 0.96

(95% CI,

0.82, 1.13)

 

HR 0.86

(95% CI,

0.74, 0.98)

 

HR 0.96

(95% CI,

0.79, 1.17)

 

No increased risk of MACE and all-cause mortality and a lower risk of MACE+ compared to epoetin alfa

  1. ID patients are those who initiated dialysis within four months prior to randomization
  2. ID patients are a subgroup of the DD patient population

The primary efficacy endpoint was achieved in the pooled analyses for NDD and DD patients, and in all individual Phase III trials. Data from the pooled efficacy and CV safety analyses, together with other statistical analyses, will form part of the regulatory submission in the US, which is anticipated in Q4 2019.

The pooled efficacy analyses in the NDD population showed roxadustat demonstrated a statistically significant mean increase from baseline in hemoglobin (Hb) levels, regardless of iron repletion, averaged over weeks 28 to 52 of 1.85 g/dL in patients treated with roxadustat compared to 0.13 g/dL with placebo (p<0.001).

The pooled efficacy analyses in the DD population showed roxadustat demonstrated a statistically significant mean increase from baseline in Hb levels averaged over weeks 28 to 52 with 1.22 g/dL in patients treated with roxadustat compared to 0.99 g/dL with epoetin alfa (p<0.001).

About roxadustat

Roxadustat is an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that has the potential to promote erythropoiesis by increasing endogenous production of erythropoietin and improving iron regulation and overcoming the negative impact of inflammation on hemoglobin synthesis and red blood cell production resulting in a downregulation of hepcidin. Use of roxadustat may coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range, in multiple subpopulations of CKD patients, including in the presence of inflammation.

About the Phase III program

FibroGen, Inc., (FibroGen) and AstraZeneca are collaborating on the development and commercialization of roxadustat for the treatment of anemia in patients with CKD in the US, China, and other global markets. FibroGen and Astellas Pharma Inc. (Astellas) are collaborating on the development and commercialization of roxadustat for the treatment of anemia in patients with chronic kidney disease (CKD) in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa.

The global Phase III program includes more than 9,000 patients and was conducted by AstraZeneca, FibroGen and Astellas together. The OLYMPUS, ALPS and ANDES trials evaluated roxadustat vs. placebo in NDD patients. ROCKIES, SIERRAS and HIMALAYAS evaluated roxadustat vs. epoetin alfa in DD patients. HIMALAYAS evaluated roxadustat vs. epoetin alfa in ID patients; there were ID patients in ROCKIES and SIERRAS. PYRENEES was not included in the pooled CV safety analyses.

About anemia

Anemia can be a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body.Anemia from CKD is associated with increased risk of hospitalization, CV complications and death, also frequently causing significant fatigue, cognitive dysfunction and decreased quality of life. Severe anemia is common in patients with CKD, cancer, myelodysplastic syndrome, inflammatory diseases and other serious illnesses.

Anemia is particularly prevalent in patients with CKD. CKD affects more than 200 million patients worldwide and is generally a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure.

According to the United States Renal Data System, about 80% of the approximately 507,000 patients receiving dialysis in the US in 2016 were being treated with erythropoiesis-stimulating agents (ESA). Patients seldom receive ESA treatment until they initiate dialysis therapy.

About AstraZeneca in CVRM

Cardiovascular, Renal & Metabolism (CVRM) together forms one of AstraZeneca’s three therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

US- 32753 Last Updated 11/19

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