Novel Agent AC01 Shows Promise in Heart Failure with Reduced Ejection Fraction: Study
Sweden: A phase Ib/IIa study published in The Lancet found that AC01, a novel oral calcium-sensitizing inotrope and ghrelin receptor agonist, was safe and well tolerated in patients with heart failure with reduced ejection fraction (HFrEF) over 28 days. With no major safety concerns identified, the findings support larger clinical trials to evaluate its efficacy and long-term safety as a potential treatment for HFrEF.
The findings are based on a study led by Prof. Lars H. Lund from the Unit of Cardiology, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, and colleagues. The researchers evaluated the safety, tolerability, pharmacokinetics, and exploratory efficacy of AC01, a novel oral calcium-sensitizing inotrope and ghrelin receptor agonist, in patients with heart failure with reduced ejection fraction.
The phase Ib/IIa randomized, double-blind, placebo-controlled trial enrolled 58 adults (median age 66 years; 91% men) with HFrEF across 14 centers in the Netherlands, the UK, Sweden, and Italy. Participants received escalating doses of AC01 or placebo for 7 days in phase Ib or one of two AC01 dose regimens or placebo for 28 days in phase IIa. Safety and tolerability were assessed through clinical evaluation, laboratory tests, electrocardiography, and continuous cardiac rhythm monitoring.
Key findings of the study include:
- AC01 was generally safe and well tolerated across all dose levels during the 28-day treatment period.
- No AC01-related serious adverse events or deaths occurred during the study.
- A treatment-related serious adverse event involving elevated high-sensitivity cardiac troponin I occurred in a patient receiving placebo, not AC01.
- Mild or moderate treatment-emergent adverse events occurred in 80% of patients receiving AC01 and 71% of those receiving placebo.
- The most frequently reported adverse events included hypotension, non-sustained ventricular tachycardia, dyspnoea, hyperglycaemia, dizziness or vertigo, and headache.
- Electrocardiographic monitoring showed no evidence of tachycardia, new-onset tachyarrhythmias, myocardial ischemia, or clinically significant conduction abnormalities.
- No cases of symptomatic hypotension were observed, and AC01 showed no apparent adverse effects on high-sensitivity cardiac troponin I or NT-proBNP levels.
The findings suggest that AC01 has a favorable short-term safety profile and may offer a promising oral treatment option for HFrEF, with no clinically significant cardiac safety signals observed during the 28-day treatment period.
The researchers acknowledged that the early-phase trial included a small number of participants and a short treatment duration and was designed primarily to assess safety and pharmacokinetics rather than clinical efficacy.
The researchers concluded that AC01 was safe and well tolerated in patients with HFrEF, with no major safety concerns identified over 28 days. They emphasized that larger, longer-term clinical trials are needed to confirm its efficacy and long-term safety.
Reference:
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. https://doi.org/10.1016/S0140-6736(26)00904-9
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