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757 Roxadustat Increases Hemoglobin in Anemic Non-Dialysis-Dependent (NDD) Chronic Kidney Disease (CKD) Patients Independent of Inflammation

Program: Oral and Poster Abstracts
Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster I
Hematology Disease Topics & Pathways:
Anemias, Adult, Diseases, Non-Biological, Therapies, Biological Processes, erythropoiesis, Study Population, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Carol A. Pollock1*, Simon Roger2*, Roberto Manllo-Karim3*, Maksym Pola4*, Stefan Tham5*, Kin-Hung P Yu, MD6* and Mohamed El-Shahawy7*

1The University of Sydney, Sydney, Australia
2Renal Unit, Gosford Hospital, Gosford, Australia
3Gamma Medical Research, McAllen, TX
4Clinical Research, AstraZeneca, Warsaw, Poland
5Clinical Research, AstraZeneca, Gothenburg, Sweden
6FibroGen Inc., San Francisco
7Keck-USC School of Medicine, Los Angeles, CA

Background: Inflammation is a common cause of decreased responsiveness to erythropoiesis-stimulating agents. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, treats anemia by inducing endogenous erythropoietin production and increasing iron utilization via reducing hepcidin. Roxadustat efficacy has been shown in those with inflammation, as defined by baseline (BL) elevation of high sensitivity C-reactive protein (hsCRP). This pooled analysis explored the efficacy of roxadustat in correcting Hb in NDD-CKD patients across the spectrum of BL hsCRP values.

Methods: Data from three randomized Phase 3 pivotal trials in anemic patients with Stage 3–5 NDD-CKD were pooled and the efficacy of roxadustat in increasing hemoglobin (Hb) from BL was assessed. hsCRP concentration was used as a marker of inflammation; patients with hsCRP >5 mg/L were considered to have inflammation at BL. Mean Hb change from BL to Weeks 28–52 was summarized by baseline hsCRP quintile. Roxadustat dose requirements at Week 24 were based on mean weekly dose in mg per kg of mean BL weight.

Results: Overall, 1691 roxadustat-treated NDD-CKD patients were assessed and had a mean BL hsCRP of 7.4 mg/L. Mean BL Hb measures were similar across the hsCRP quintiles (range 9.0–9.2 g/dL). In patients with BL inflammation (n=523), mean Hb change from baseline to Weeks 28–52 was 1.95 g/dL with roxadustat. Mean Hb change from baseline to Weeks 28–52 was also similar across all hsCRP quintiles in roxadustat-treated patients (Figure). Mean weekly roxadustat doses at Week 24 for baseline hsCRP quintiles 1 through to 5 were comparable at 3.2, 2.9, 2.5, 3.0, and 3.0 mg/kg, respectively.

Conclusion: Roxadustat increased Hb in anemic NDD-CKD patients independent of inflammation.

Disclosures: Pollock: Otsuka Pharmaceuticals: Consultancy; Novartis: Consultancy; Johnson and Johnson: Consultancy; AstraZeneca: Consultancy; FibroGen: Consultancy; Eli Lilly and Company: Consultancy; Janssen Cilag: Consultancy. Manllo-Karim: FibroGen Inc.: Current equity holder in private company. Pola: AstraZeneca: Current Employment, Current equity holder in private company. Tham: AstraZeneca: Current Employment, Current equity holder in private company. Yu: FibroGen Inc.: Current Employment, Current equity holder in private company. El-Shahawy: AstraZeneca: Consultancy, Research Funding.

*signifies non-member of ASH