AnaCardio Phase 1b/2a heart failure data published in The Lancet
AnaCardio has announced that results from its Phase 1b/2a GOAL-HF1 study of AC01 in heart failure with reduced ejection fraction have been published in The Lancet. The Stockholm-based biopharmaceutical company said the study met its primary objectives of safety and tolerability, and recorded exploratory efficacy signals that the company believes justify advancing to Phase 2b development.
AC01 is described by AnaCardio as a first-in-class oral calcium-sensitising contractile agent and ghrelin receptor agonist, originally in-licensed from Swiss oncology and speciality pharma group Helsinn. The drug's mechanism differentiates it from traditional inotropic agents, which have historically been limited by proarrhythmic and ischaemic side effects that have prevented their chronic use.
Trial design and key findings
GOAL-HF1 was a multicentre, randomised, double-blind, placebo-controlled study across 14 sites in the Netherlands, the United Kingdom, Sweden, and Italy, enrolling 58 patients with NYHA class II to III HFrEF. All participants had a mean ejection fraction of 31.4% and were on maximum tolerated guideline-directed medical therapy, a design choice that raises the bar for detecting an incremental treatment signal.
The Phase 1b component tested multiple ascending doses in 32 patients (0.1 to 3 mg twice daily over seven days). In the Phase 2a portion, 26 patients were randomised equally to 1 mg AC01, 3 mg AC01, or placebo twice daily for 28 days. The company reported no AC01-related serious adverse events, no deaths, no treatment discontinuations due to adverse events, and no evidence of tachycardia, new-onset arrhythmias, myocardial ischaemia, or symptomatic hypotension.
On the exploratory efficacy side, improvements in cardiac output and stroke volume were observed from day one and sustained through day 28. Left ventricular ejection fraction increased by a mean of 4.8 absolute percentage points at day 28 in the 3 mg group, compared with 1.6 percentage points in the placebo group. The company has been clear that these are exploratory, not powered, analyses.
Professor Lars Lund, cardiologist at Karolinska University Hospital and founder of AnaCardio, said the results "provide a strong foundation to guide late-stage clinical trials, and hold real promise to translate into meaningful benefits for patients in terms of mortality, morbidity, and quality of life."
Market context and competitive landscape
Heart failure with reduced ejection fraction is one of the most significant unmet clinical needs in cardiology, affecting tens of millions of patients globally. Despite well-established pillars of guideline-directed therapy including ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, meaningful cardiac contractility improvement without the baggage of traditional inotrope toxicity has remained elusive.
Several companies are pursuing novel inotropic and cardiac myosin-activating mechanisms in this space. Bristol Myers Squibb's omecamtiv mecarbil, a cardiac myosin activator, completed a large Phase 3 study (GALACTIC-HF) but showed a modest and controversial overall survival benefit, illustrating the difficulty of translating haemodynamic gains into hard clinical endpoints. AnaCardio's ghrelin-mimetic approach is mechanistically distinct, and the favourable safety profile observed in GOAL-HF1 is the company's primary differentiating claim at this stage.
AnaCardio has raised over USD 40 million to date and said it has received positive scientific advice from both the FDA and EMA on its Phase 2b development path. The company is privately held, so further financing will be required to fund the larger, longer trial needed to generate the mortality and hospitalisation data that regulators and payers will ultimately require. Investors and collaborators will be watching the Phase 2b design, patient numbers, and primary endpoint selection closely as the next critical milestones for the programme.