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Background <p>Non-transfusion-dependent beta-thalassemia (β-NTDT) is characterized by ineffective erythropoiesis, increased intestinal iron absorption, and iron overload. The ferroportin inhibitor, vamifeport, has been shown to improve erythropoiesis via decreases in serum iron and transferrin saturation levels in preclinical models and healthy volunteer studies.</p> Objective <p>The objective of this 12-week, double-blind, randomized, placebo-controlled, phase 2a study was to assess the safety and tolerability of vamifeport versus placebo in adults with β-NTDT (primary endpoint). Iron-related pharmacodynamic effects (preliminary efficacy) were also assessed as a secondary endpoint.</p> Methods <p>Randomized, adult patients weighing 40–59&#xa0;kg and 60–100&#xa0;kg received vamifeport 60&#xa0;mg and 120&#xa0;mg (once [QD] or twice [BID] daily), respectively, for 12 weeks. Non-transfusion-dependent thalassemia was defined as transfusion requirements &lt; 5 units of red blood cells during the 24 weeks before randomization.</p> Results <p>Twenty-five patients were included (vamifeport QD <i>n</i> = 9, BID <i>n</i> = 12; placebo <i>n</i> = 4); 64% were male and 56% weighed &lt; 60&#xa0;kg. Baseline serum iron and transferrin saturation levels were similar across treatment groups. All treatment-emergent adverse events were mild/moderate, and rates were similar across groups (vamifeport QD 67%, BID 58%; placebo 75%). There were no deaths or serious treatment-emergent adverse events and no clinically relevant changes in safety parameters. Serum iron and transferrin saturation levels decreased by 2&#xa0;h after the first vamifeport dose (mean [standard deviation] decreased QD − 12.2 [6.5], BID − 14.5 [12.1] µmol/L and QD − 33.6 [18.9], BID − 37.2 [27.6] %, respectively) and remained below baseline levels at each subsequent visit. There were no clinically meaningful changes in the placebo group.</p> Conclusion <p>In this 12-week study, vamifeport had a favorable safety/tolerability profile, with no changes in hemoglobin levels ≥ 1.0&#xa0;g/dL, and promising pharmacodynamic effects versus placebo in adults with β-NTDT.</p> Trial registration <p>ClinicalTrials.gov, NCT04364269. Registered 01 April 2020; Prospectively registered, <a href="https://clinicaltrials.gov/study/NCT04364269?term=NCT04364269&amp;rank=1">https://clinicaltrials.gov/study/NCT04364269?term=NCT04364269&amp;rank=1</a>.</p>

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Safety and pharmacodynamics of the ferroportin inhibitor vamifeport in patients with non-transfusion-dependent β-thalassemia: results from a randomized phase 2a study

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  • 发表日期：

    2025年11月25日

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  • Antonis Kattamis,
  • Ali Taher,
  • Vip Viprakasit,
  • Carina Levin,
  • Ricardo Hermosilla,
  • Peter Szecsödy,
  • Frank Richard,
  • M. Domenica Cappellini,
  • John Porter

摘要

Background

Non-transfusion-dependent beta-thalassemia (β-NTDT) is characterized by ineffective erythropoiesis, increased intestinal iron absorption, and iron overload. The ferroportin inhibitor, vamifeport, has been shown to improve erythropoiesis via decreases in serum iron and transferrin saturation levels in preclinical models and healthy volunteer studies.

Objective

The objective of this 12-week, double-blind, randomized, placebo-controlled, phase 2a study was to assess the safety and tolerability of vamifeport versus placebo in adults with β-NTDT (primary endpoint). Iron-related pharmacodynamic effects (preliminary efficacy) were also assessed as a secondary endpoint.

Methods

Randomized, adult patients weighing 40–59 kg and 60–100 kg received vamifeport 60 mg and 120 mg (once [QD] or twice [BID] daily), respectively, for 12 weeks. Non-transfusion-dependent thalassemia was defined as transfusion requirements < 5 units of red blood cells during the 24 weeks before randomization.

Results

Twenty-five patients were included (vamifeport QD n = 9, BID n = 12; placebo n = 4); 64% were male and 56% weighed < 60 kg. Baseline serum iron and transferrin saturation levels were similar across treatment groups. All treatment-emergent adverse events were mild/moderate, and rates were similar across groups (vamifeport QD 67%, BID 58%; placebo 75%). There were no deaths or serious treatment-emergent adverse events and no clinically relevant changes in safety parameters. Serum iron and transferrin saturation levels decreased by 2 h after the first vamifeport dose (mean [standard deviation] decreased QD − 12.2 [6.5], BID − 14.5 [12.1] µmol/L and QD − 33.6 [18.9], BID − 37.2 [27.6] %, respectively) and remained below baseline levels at each subsequent visit. There were no clinically meaningful changes in the placebo group.

Conclusion

In this 12-week study, vamifeport had a favorable safety/tolerability profile, with no changes in hemoglobin levels ≥ 1.0 g/dL, and promising pharmacodynamic effects versus placebo in adults with β-NTDT.

Trial registration

ClinicalTrials.gov, NCT04364269. Registered 01 April 2020; Prospectively registered, https://clinicaltrials.gov/study/NCT04364269?term=NCT04364269&rank=1.