The American Society of Nephrology (ASN) Kidney Week 2017 was held in New Orleans in early November 2017. Presentations related to iron deficiency and anaemia provided updates on both benefits and risks with current available therapies. Presenters also discussed treatments under development, particularly those that focus on activating the Hypoxia-Inducible Factor (HIF) pathway.
Benefits of anaemia treatment
The main clinical practice session on anaemia, Therapeutic Options for Anemia Management in CKD, was chaired by Drs Kovesdy and Wish, USA. Topics covered included:
- The current approach to managing anaemia and the impact of reimbursement changes, among other drivers, on US clinical practice.
- The benefits of IV iron therapy, such as reduced ESA dosing and potential improvements in quality of life, alongside concerns regarding high doses of iron potentially overwhelming normal homeostatic mechanisms and leading to complications.
- The potential for significant cost savings in the US if the use of biosimilar ESA is approved by the FDA.
Several studies also examined associations between patient outcomes and both iron deficiency and anaemia. A series of posters reported on historical cohort studies of over 1.1m US veterans with CKD, in which 83,570 veterans with non-dialysis-dependent CKD (NDD-CKD), for whom iron indices were available, were grouped into cohorts based on their ferritin and TSAT levels. The analysis found that
- “Functional iron deficiency was associated with the highest all-cause mortality risk”
- “Increased iron status was associated with increased risk for incident ESRD”
- “Diabetes status did not alter the association between iron status and ESRD risk”
On a similar theme, analysis of data from 3,919 patients in the Chronic Renal Insufficiency Cohort (CRIC) study found that anaemia was “independently associated with increased risk for incident ESRD but not all-cause death.”
Safety of IV iron therapies
Several clinical studies presented at Kidney Week 2017 examined the safety of IV iron therapies.
- A UK-based observational study of two IV iron formulations found two anaphylactic reactions in over 2,100 doses to NDD-CKD patients, with both reactions occurring in the same patient. The authors concluded that, while vigilance is necessary during the administration of IV iron to non-dialysis CKD patients, “the balance between the benefits and the risks remains in favour of intravenous iron administration.”
- Treatment with ferric carboxymaltose may lead to an increased incidence of hypophosphatemia, according to a study presented by Dr Myles Wolf. The presented data was derived from a subanalysis of a clinical trial of ferumoxytol in adults with iron deficiency anaemia, including some adults who had CKD. The investigators stated that further studies are needed to investigate this finding further.
- A pilot program examining potential oxidative stress following administration of three different IV iron formulations found no acute effect of IV iron on endothelial function, although the authors are conducting further analysis on the data to assess any additional effects.
Looking to the future: novel therapies
Several symposia and posters presented information on a novel mechanism of action (MoA) for correcting anaemia: stabilizing HIF. Several therapies with this MoA are currently in late-stage development.
Oral presentations discussed how hypoxia in cells stimulates erythropoiesis by increasing erythropoietin production, while also improving enteric iron absorption and transport. Presenters outlined how stabilizing HIF may have the effect of activating the same erythropoietic process, although presenters also highlighted that new therapies with this MoA would need rigorous safety analysis.
Poster sessions featured data from three molecules targeting the HIF pathway, with studies showing improved haemoglobin levels in both dialysis and non-dialysis settings, following treatment with these molecules.[8,9,10]
Data was also presented on ferric citrate, an oral, iron-based, phosphate binder that, at the time of the conference, was under review by the FDA for the treatment of iron deficiency anaemia in adults with NDD-CKD. One presentation suggested that treatment with ferric citrate may reduce FGF23 levels in NDD-CKD patients, while analysis of real-world data found that patients prescribed ferric citrate had mean increases in haemoglobin, TSAT, and ferritin over time, despite decreases in cumulative IV iron and ESA doses. An industry-sponsored educational symposium also provided information on the positive impact of ferric citrate on iron parameters in patients with CKD. The potential for ferric citrate to induce iron overload was also discussed in the question and answer session of this symposium.
- Therapeutic Options for Anemia Management in CKD. ASN Kidney Week 2017
- Iron Status and Mortality Risk in Diabetic and Non-Diabetic Veterans with CKD. Cho M. et al. ASN Kidney Week 2017, FR-PO519
- Iron Status and the Risk of Incident ESRD in Veterans with CKD. Cho M. et al. ASN Kidney Week 2017, FR-PO520
- Anemia Is a Risk Factor for Incident ESRD. Saraf S. et al. ASN Kidney Week 2017, FR-PO391
- Review of Safety of IV Iron Therapy in Patients with Non-Dialysis CKD (CKD-ND). Meyer V. et al. ASN Kidney Week 2017, FR-PO522
- Occurrence of Hypophosphatemia Following IV Iron Treatment: Results from a Randomized Controlled Trial. Wolf M. et al. ASN Kidney Week 2017, FR-OR071
- Prospective Comparative Pilot Study of the Short-Term Efficacy and Oxidative Stress Effects of Various IV Iron Therapies in Iron Deficient CKD Patients. Zerdan A. et al. ASN Kidney Week 2017, TH-PO498
- DIALOGUE Phase 2 extension studies of BAY 85-3934, Molidustat, a HIF-PH inhibitor with Daily Oral Treatment in Anemic Subjects with CKD. Akizawa T. et al. ASN Kidney Week 2017, FR-PO1070
- A 29-Day Safety, Efficacy, and Pharmacodynamic Study of a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, Daprodustat, Administered TIW in Anemic Subjects on Hemodialysis (HD). Bailey C. et al. ASN Kidney Week 2017, SA-PO811
- Roxadustat Treatment of CKD Anemia Is Not Influenced by Inflammation. Szczech L. et al. ASN Kidney Week 2017, SA-PO827
- Ferric Citrate Reduced FGF23 in Patients with Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) and Iron Deficiency Anemia Irrespective of the Change in Serum Phosphate. Block G. et al. ASN Kidney Week 2017, TH-OR038
- The Effect of Ferric Citrate on IV Iron, ESA Utilization, and Laboratory Parameters in Real-World Dialysis Practice. Kovesdy C. et al. ASN Kidney Week 2017, SA-PO825
- Ferric citrate prescribing information. FDA.