New study shows that treatment with ferric derisomaltose improves exercise capacity in patients with heart failure with preserved ejection fraction and iron deficiency

Iron deficiency affects 50% of people with heart failure and is associated with reduced exercise capacity and poorer quality of life1. Heart failure affects approximately 1–2% of adults in developed countries, with prevalence increasing markedly with age2.

IRONMET-HFpEF focused on patients with iron deficiency and HFpEF (~50% of all HF patients3), a form of heart failure in which the heart pumps out a normal proportion of blood with each beat but can have difficulty relaxing and filling between beats, resulting in fluid congestion. Patients commonly experience breathlessness and difficulty with physical activity, including everyday tasks such as walking or climbing stairs4.

The IRONMET-HFpEF study, sponsored by the National Institutes of Health and conducted at Massachusetts General Hospital in Boston, investigated whether correcting iron deficiency with ferric derisomaltose, an intravenous iron treatment developed and manufactured by Pharmacosmos, could improve exercise capacity in these patients. It enrolled 65 patients at a single center and compared ferric derisomaltose with placebo over 12 weeks. The main measure was peak oxygen uptake, the highest amount of oxygen the body uses during an exercise test. Peak oxygen uptake is a key measure of heart failure disease burden that objectively captures the burden of functional limitation experienced by people with HFpEF.

At 12 weeks, the adjusted difference between groups in the change in peak oxygen uptake was 1.1 mL/kg/min in favor of ferric derisomaltose (95% confidence interval [CI], 0.2 to 1.9; P=0.02). Patients receiving ferric derisomaltose also showed a greater improvement in the distance walked in six minutes, with a between-group difference of 41.1 meters (95% CI, 9.5 to 72.8; P=0.01).

"In the first study to comprehensively evaluate exercise response patterns to iron repletion in patients with HFpEF and iron deficiency, we found that ferric derisomaltose improved multiple measures of exercise capacity," said principal investigator Gregory Lewis, MD, Director of Heart Failure, Mass General Brigham Heart and Vascular Institute and Professor of Medicine, Harvard Medical School.

Few studies have examined intravenous iron in HFpEF. IRONMET-HFpEF represents a step towards understanding whether correcting iron deficiency can improve exercise capacity in this less studied patient group.

"The improvement we observed in peak VO2 represents a clinically meaningful increment for patients with heart failure," said co-principal investigator Rajeev Malhotra, MD, Associate Director of the Cardiopulmonary Exercise Laboratory at the Mass General Brigham Heart and Vascular Institute and Associate Professor of Medicine at Harvard Medical School.

Research into iron deficiency across different heart failure populations includes Pharmacosmos’ support for IRONMAN and its ongoing international Phase III trial, ICONIC-HF, involving clinical sites across Europe, Latin America, Asia, Canada and the United States.

About the study

IRONMET-HFpEF was an investigator-initiated, National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled trial conducted at Massachusetts General Hospital in Boston. Sixty-five adults with HFpEF and iron deficiency were randomised 2:1 to receive a single 1,000 mg intravenous dose of ferric derisomaltose or placebo. The primary endpoint was change in peak oxygen uptake from baseline to week 12. The study included participants with and without anemia and was registered at ClinicalTrials.gov (NCT04945707). The results were presented November 8 in a Late-breaking Science Session at the American Heart Association Scientific Sessions 2026 in Chicago and published simultaneously in Circulation. Link

The findings are limited by the sample size of 65 patients, single-center design and 12-week follow-up. KCCQ did not differ significantly between groups, and the study was not designed to assess longer-term outcomes such as hospitalization or mortality. In this study, no serious adverse events were related to ferric derisomaltose.

Pharmacosmos donated the study drug.

About Pharmacosmos

Pharmacosmos A/S is a global leader in carbohydrate chemistry and innovative treatments for iron deficiency and iron deficiency anemia. Building on our foundational expertise in carbohydrate chemistry and cell cycle biology, we develop innovative treatments for unmet patient needs, with a focus on iron metabolism and blood-related disorders. Founded in 1965 and headquartered in Denmark, our team is made up of more than 650 specialists across the UK, Ireland, the Nordics, Germany, Canada, and the USA.

Contact

Christian Lundquist Madsen, Vice President Global Marketing & Communication
+45 5948 5959 | clm@pharmacosmos.com

1. Lewis G, et al. Circulation 2026, DOI: 10.1161/CIRCULATIONAHA.126.084009

2. Khan MS, et al. Nat Rev Cardiol. 2024 for overall HF epidemiology

3. Campbell P, Rutten FH, Lee MMY, Hawkins NM, Petrie MC. Heart failure with preserved ejection fraction: everything the clinician needs to know. The Lancet. 2024;403:1083–1092

4. Ejection Fraction Heart Failure Measurement | American Heart Association