Clinical Trials Arena

Cardurion’s PDE9 inhibitor increases cGMP in Phase IIa heart failure trial

Caudrion said the Phase IIa trial has proved that targeting PDE9 activates the NP signalling pathway.

Cardurion Pharmaceuticals has said its phosphodiesterase-9 (PDE9) inhibitor, CRD-740, has met the primary endpoint of its Phase IIa study in heart failure patients.

The CARDINAL-HF Phase IIa trial (NCT05409183), CRD-740 met the primary endpoint in heart failure patients with reduced ejection fraction (HFrEF), demonstrating a statistically significant median increase in plasma cyclic guanosine monophosphate (cGMP), reflecting the increased activation of the myocardial natriuretic peptide (NP) signalling pathway.

This confirms that targeting PDE9 activates the NP signalling pathway, a highly validated pathway with established clinical benefits. CRD-740 was generally well-tolerated in patients with HFrEF.

Increases in plasma and urinary cGMP were observed in patients who received CRD‑740 with and without background treatment with sacubitril/valsartan, supporting the potential for CRD-740 as both a monotherapy and in combination with sacubitril and valsartan.

Based on the results from CARDINAL-HF, Cardurion has launched two Phase II trials in 640 patients, including a dose-ranging trial in patients with HFrEF and a proof-of-concept trial in patients with heart failure with preserved ejection fraction (HFpEF).

Part A of the trial was completely successful. However, according to ClinicalTrials.gov, the second part was terminated in favour of a new study design.

Cardurion's CEO Peter Lawrence said: “The data from this trial suggest that PDE9 inhibition has the potential to provide benefit to patients when administered alone or in combination with guideline-directed medical therapy, and ultimately become standard of care for patients with both types of heart failure.”

Heart failure landscape

Heart failure is a multi-faceted and life-threatening syndrome with significant morbidity and mortality, poor functional capacity and quality of life, and high costs. The prevalence of heart failure is on the rise due to the ageing global population and the increased prevalence of risk factors such as diabetes, obesity, and hypertension.

Treatment options for heart failure include lifestyle changes such as reducing sodium intake, maintaining a healthy weight, regular physical activity, quitting smoking, avoiding alcohol, and managing stress.

Medications and medical devices may also be prescribed to manage the condition.