Safety and Efficacy of Oral Ferric Maltol and Ferrous Sulfate for Iron Deficiency Anemia in Infants, Children and Adolescents: A Multicenter Randomized Trial.

Abstract

Objectives: This phase 3, multicenter, randomized, open-label study (NCT05126901) compared oral ferric maltol with ferrous sulfate, across 23 sites in the US and the UK, evaluating the safety, efficacy, pharmacokinetics, tolerability, and palatability of age-specific doses in infants, children and, adolescents with iron deficiency anemia (IDA).

Patient and methods: In a 12-week study, a total of 61 children/adolescents aged 2-17 years (median age 14 years; 45 female patients [73.8%] and 16 male patients [26.2%]) with IDA were randomized to ferric maltol or ferrous sulfate, plus 4 infants aged 1 month to < 2 years (median age 12 months; 3 female patients [75%] and 1 male patient [25%]) were assigned to ferric maltol (open label arm). Ferric maltol dosing was age-dependent (0.6 mg/kg/dose twice a day [BID] for infants; 15 mg BID for 2-11 years; 30 mg BID for 12-17 years), while ferrous sulfate dosing was weight-based (3 mg/kg BID). Safety, efficacy (Hemoglobin [Hb], serum iron, transferrin saturation [TSAT], ferritin), PK, and palatability were assessed. Coprimary end points were Hb changes from baseline and safety, including gastrointestinal tolerability at week 12.

Results: A prespecified interim analysis of the primary end point (change in Hb from baseline to week 12) was conducted after 32 ferric maltol patients completed treatment. As the change was statistically significant (p < 0.0001), recruitment was stopped. The interim analysis used a Pocock spending function with a 3.45% two-sided confidence interval (CI). Both the randomized ferric maltol and ferrous sulfate groups showed meaningful increases in Hb versus baseline (descriptive increases of 1.25 and 1.15 g/dL, respectively). Post hoc analyses confirmed that these changes from baseline were statistically significant (p < 0.0001). Ferric maltol increased Hb by a mean of 1.77 g/dL in the assigned infant group over 12 weeks. Similarly, by week 12, both treatments increased serum iron and TSAT (p < 0.02), ferric maltol showed higher peak iron, and ferritin rose more with ferrous sulfate. Adverse events were mild/moderate and similar in frequency between the two treatment groups (29% ferric maltol, 30% ferrous sulfate), and adverse reactions deemed as at least possibly related to treatment were more common with ferrous sulfate. Among children aged 6-17 years, ferric maltol was rated as tasting OK, Good, or Very Good more frequently than ferrous sulfate at two time points. On day 1, 79.3% of patients receiving ferric maltol reported OK, Good, or Very Good taste, compared with 50.0% receiving ferrous sulfate (OR 0.26, 95% CI 0.07-0.97; p = 0.027). By day 28, this difference persisted (75.0% versus 45.8%), favoring ferric maltol (OR 0.28, 95% CI 0.07-1.05; p = 0.046). The significant results for taste were replicated for smell; ferric maltol had significantly better smell ratings than ferrous sulfate on days 1 and 28 (p ≤ 0.003).

Conclusions: Ferric maltol significantly improved Hb levels and iron storage within 12 weeks in children aged 1 month and above, offering potentially better tolerability and palatability compared with ferrous sulfate in children and adolescents.