Kidney Week

Abstract: TH-PO875

Effects of Interleukin-6 Inhibition with Clazakizumab on Anemia and Iron Parameters in Patients with Kidney Failure

Session Information

• Anemia and Iron Metabolism
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Neuen, Brendon Lange, The George Institute for Global Health, Sydney, New South Wales, Australia

Brendon Lange Neuen, MBBS, MS, PhD, FASN

• Wolf, Myles, Duke University School of Medicine, Durham, North Carolina, United States

Myles Wolf, MD, MMSc

• Catanese, Benjamin Peter, Duke University School of Medicine, Durham, North Carolina, United States

Benjamin Peter Catanese, MD

• Heise, Mark A., CSL Behring LLC, King of Prussia, Pennsylvania, United States

Mark A. Heise, PhD

• Tricoci, Pierluigi, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Pierluigi Tricoci, MD, MS, MSc, PhD

• Chang, Anna Marie, CSL Behring LLC, King of Prussia, Pennsylvania, United States

Anna Marie Chang, MD, MS

• Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

Background

Inflammation contributes to anemia and erythropoietin stimulating agent resistance in patients with kidney failure. Clazakizumab is a high affinity humanized monoclonal antibody that targets the interleukin-6 (IL-6) ligand and inhibits downstream IL-6 function. We recently reported an approximate 90% reduction in high-sensitivity C-reactive protein (hs-CRP) in patients receiving dialysis with a history of cardiovascular disease and/or diabetes. We sought to evaluate the effect of clazakizumab on anemia and iron parameters.

Methods

The Phase 2b component of the POSIBIL₆ESKD Phase 2b/3 trial evaluated the effect of clazakizumab (2.5mg, 5mg, 10mg) or placebo administered every 4 weeks. The primary efficacy endpoint was the placebo-adjusted change in hs-CRP at 12 weeks. We prespecified as secondary endpoints the effects of clazakizumab on hemoglobin (Hb), iron parameters, and hepcidin, using mixed effects models for repeated measures.

Results

Among 127 participants, overall mean ± SD Hb and TSAT, median (25%, 75% range) ferritin and hepcidin were 10.7 ± 1.4 g/dL, 31 ± 11.7%, 1267 (735, 1598) µg/L and 232 (150, 306) ng/mL, respectively. The mean increase in Hb was 0.6 ± 1.5, 1.0 ± 1.3, 1.0 ± 1.4 g/dL at 12 weeks relative to baseline in the 2.5, 5, and 10 mg clazakizumab groups, respectively, compared with 0.4 ± 1.3 g/dL with placebo. These differences were not statistically significant. Clazakizumab significantly increased transferrin saturation and reduced hepcidin across all studied doses versus placebo, and had no clear effect on ferritin (Figure).

Conclusion

Through anti-IL6 effects, clazakizumab may improve iron utilization and contribute to anemia correction in patients receiving dialysis. Larger and longer-term data from the ongoing Phase 3 study will provide additional insights.

Funding

• Commercial Support – CSL Behring