Ghrelin Receptor Agonist AC01 Shows Safety and Hemodynamic Promise in Early Heart Failure Trial
核心洞察
A phase 1b/2a trial of oral AC01 in 58 patients with chronic heart failure (搜索) with reduced ejection fraction demonstrated safety and tolerability with no serious drug-related adverse events.
AC01 targets the ghrelin receptor (搜索) via a novel mechanism distinct from traditional inotropes, aiming to strengthen cardiac contractility without causing heart rhythm disturbances or blood pressure changes.
Exploratory analyses showed signals of improved heart function, including increased stroke volume and cardiac output, warranting larger and longer confirmatory studies.
An early-stage clinical trial has found that AC01, a novel oral drug targeting the ghrelin receptor (搜索), is safe and well-tolerated in patients with chronic heart failure (搜索) with reduced pumping capacity, according to results published in The Lancet. The randomized, double-blind, placebo-controlled phase 1b/2a study, led by researchers at Karolinska Institutet, also yielded exploratory signals of improved cardiac function, setting the stage for larger investigations.
The trial enrolled 58 patients with stable, chronic heart failure (搜索) with reduced ejection fraction across multiple European centers. Participants were randomized to receive different doses of AC01 or placebo for either seven or 28 days, with safety and tolerability serving as the primary objectives.
A Novel Mechanism to Strengthen the Heart
AC01 acts as an agonist at the ghrelin receptor (搜索), a target also expressed in heart muscle. Ghrelin, a hormone known for its role in metabolism and growth hormone release, represents a departure from conventional inotropic agents. Existing drugs that enhance cardiac contractility can provoke serious adverse effects, including heart rhythm disturbances and deleterious blood pressure changes. AC01 is designed to strengthen the heart's pumping ability through a distinct biological pathway, potentially mitigating these risks.
"The results show that the drug was well tolerated. No serious side effects linked to AC01 were reported," the investigators noted. Importantly, the study detected no signs of harmful effects on heart rhythm or blood pressure, addressing a key safety concern associated with traditional heart-stimulating medications.
Exploratory Efficacy Signals
Beyond the primary safety endpoints, exploratory analyses indicated signs of improved heart function. Researchers observed increases in stroke volume and cardiac output among participants receiving AC01. These hemodynamic improvements, while preliminary, provide a rationale for further clinical development.
Lars Lund, first author and professor at the Department of Medicine, Solna, Karolinska Institutet, and senior consultant cardiologist at Karolinska University Hospital, emphasized the study's early nature: "This is an early study with a limited number of patients, but the results suggest that AC01 can be administered safely to people with heart failure. The findings now justify further studies to investigate whether the signals of improved heart function that we have observed can lead to clinical benefit in larger and longer studies."
Study Design and Funding
The trial was conducted as a collaboration among researchers and clinicians across several European countries. Funding was provided by AnaCardio AB, the pharmaceutical company developing AC01. The published article discloses that several researchers, including the principal investigator, have ties to the company.
The full publication, titled "Safety, tolerability, and haemodynamic effects of the ghrelin receptor (搜索) agonist AC01 in patients with chronic heart failure (搜索): a randomised, double-blind, placebo-controlled, phase 1b/2a study," appeared online in The Lancet on June 24, 2026.