Oral Calcium-Sensitizing Inotrope AC01 Demonstrates Favorable Tolerability and Hemodynamics in Heart Failure

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Data Quality: STRONG
Summary of  The Lancet https://doi.org/10.1016/S0140-6736(26)00904-9
Dr. Prof Lars H Lund  et al.

Points

A randomized double-blind Phase Ib/IIa trial evaluated the safety and tolerability of a novel oral ghrelin receptor agonist and calcium-sensitizing inotrope named AC01.
The multicenter European study enrolled 58 patients with stable chronic heart failure with reduced ejection fraction to receive active treatment or placebo for 7 or 28 days.
Primary safety endpoints showed the trial drug was well tolerated with zero serious drug-related adverse events or harmful impacts on heart rhythm and blood pressure.
Exploratory hemodynamic assessments revealed positive signals of improved cardiac contractility evidenced by noticeable increases in patient stroke volume and total cardiac output.
Principal investigator Lars Lund indicated these early data justify larger clinical trials to fully evaluate if the observed hemodynamic benefits translate into definitive long-term clinical outcomes.

Summary

Double-blind, placebo-controlled Phase Ib/IIa trial evaluated the safety, tolerability, and exploratory hemodynamic efficacy of AC01, a novel oral calcium-sensitizing inotrope and ghrelin receptor agonist, in 58 patients presenting with stable, chronic heart failure with reduced ejection fraction (HFrEF). Given that conventional inotropic therapies often cause severe adverse events like tachyarrhythmias and arterial blood pressure fluctuations, alternative agents are clinically necessary. The study investigated whether targeting cardiac ghrelin receptors could successfully enhance myocardial contractility without triggering these conventional side effects.

Conducted as a multicenter European collaboration, the trial randomized the 58 participants to receive either varying doses of oral AC01 or a matching placebo across treatment durations of 7 or 28 days. Safety monitoring established that AC01 was well tolerated throughout the study window, with no serious drug-related adverse events reported. Crucially, serial assessments revealed zero signal of proarrhythmic activity or deleterious hemodynamic variations affecting systemic blood pressure. (Note: Specific confidence intervals and hazard ratios were not included in the primary source dataset).

Exploratory efficacy endpoints demonstrated favorable surrogate physiological signs of improved myocardial performance. Patients treated with active AC01 exhibited increases in both stroke volume and overall cardiac output compared to the placebo cohort. These initial findings indicate that the unique mechanical pathway of AC01 achieves safe, targeted inotropic support, validating the deployment of larger, longer-term clinical trials to definitively establish its long-term survival and clinical outcomes in the HFrEF population.

Link to the article: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00904-9/abstract

References

Lund, L. H., Barandiarán Aizpurua, A., Bollano, E., Braun, O., Brouwer, J. L. P., Buikema, J. W., Cannata, A., Gardner, R. S., Handoko, M. L., Lang, C. C., Metra, M., Sinagra, G., Thorvaldsen, T., Van Der Boon, R. M. A., Van Essen, B. J., Shah, S. J., Voors, A. A., Lam, C. S. P., Pitt, B., … Petrie, M. C. (2026). Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (Goal-hf1): A randomised, double-blind, placebo-controlled, phase 1b/2a study. The Lancet, S0140673626009049. https://doi.org/10.1016/S0140-6736(26)00904-9