Rationale & Objective Iron-deficiency anemia is common in patients with chronic kidney disease (CKD) not requiring kidney replacement therapy (KRT). We evaluated effects of oral iron replacement therapy with ferric maltol in these patients. Study Design Phase 3, double-blind, randomized, placebo-controlled trial (AEGIS-CKD) and open-label extension. Setting & Participants Adults with stage 3 or 4 CKD and iron-deficiency anemia at 30 US centers. Intervention Oral ferric maltol at 30 mg or placebo twice daily for 16 weeks (2:1 randomization) followed by ferric maltol at 30 mg twice daily for up to 36 weeks (all patients). Outcome Change from baseline in hemoglobin (primary end point at week 16), ferritin, transferrin saturation, and serum iron; safety. Results 167 patients were randomized (ferric maltol, n = 111; placebo, n = 56). At week 16, hemoglobin had increased significantly with ferric maltol versus placebo (least-squares mean difference: 0.5 ± 0.2 [SE] g/dL; 95% CI, 0.1-0.9; P = 0.01). Ferritin, transferrin saturation, and serum iron increased with ferric maltol but declined with placebo (all P < 0.05). Hemoglobin levels were sustained up to week 52 in patients continuing ferric maltol and increased in patients switching from placebo to ferric maltol. The most frequent adverse events were gastrointestinal (randomized phase: 41% vs 30% [ferric maltol vs placebo]; open-label phase: 56% vs 46%, respectively). Adverse events led to treatment withdrawal in 7 patients (6%) receiving ferric maltol and 5 patients (9%) receiving placebo during double-blind treatment, and 11 patients (9%) during the open-label extension. Limitations Heterogeneity in baseline ferritin levels; high proportion of female participants; single-arm open-label extension. Conclusions Ferric maltol was associated with statistically significant (week 16) and sustained (up to week 52) increases in hemoglobin and iron indices in patients with CKD and iron deficiency, and was well tolerated during treatment for up to 52 weeks. Funding Funded by Shield Therapeutics (UK) Ltd. Trial Registration Registered at ClinicalTrials.gov with study number NCT02968368.

Iron deficiency is the most common cause of anemia globally and is frequently reported in patients with underlying inflammatory conditions, such as inflammatory bowel disease (IBD) and chronic kidney disease (CKD). Ferric maltol is a new oral iron replacement therapy designed to optimize iron absorption while reducing the gastrointestinal adverse events associated with unabsorbed free iron. Ferric maltol has been studied in clinical trials involving almost 750 adults and adolescents with iron-deficiency anemia associated with IBD, CKD, and other underlying conditions, and it has been widely used in clinical practice. It is approved for the treatment of adults with iron deficiency with or without anemia, independent of the underlying condition, and is commercially available in Europe and the United States. We review the published evidence for ferric maltol, which demonstrates consistent and clinically meaningful improvements in hemoglobin and measures of iron availability (ferritin and transferrin saturation) and shows that it is well-tolerated over long-term treatment for up to 64 weeks—an important consideration in patients with chronic underlying conditions such as IBD and CKD. We believe that ferric maltol is an effective, convenient, and well-tolerated treatment option for iron deficiency and iron-deficiency anemia, especially when long-term management of chronic iron deficiency is required. Writing support was provided by Shield Therapeutics (Gateshead, UK).