Cardurion Pharmaceuticals has achieved a significant milestone by completing enrollment in two global Phase 2 clinical trials evaluating CRD-750, marking the first time a phosphodiesterase 9 (PDE9) inhibitor has entered clinical testing for chronic heart failure treatment. The Burlington, Massachusetts-based biotechnology company announced the completion of enrollment across both major heart failure subtypes, representing a novel therapeutic approach for a condition affecting 6.7 million adults in the United States.
Novel Mechanism Targets Validated Pathway
CRD-750 is an orally-administered PDE9 inhibitor designed to enhance the natriuretic peptide signaling (NPS) pathway, a clinically-validated therapeutic target for heart failure treatment. The drug represents a new mechanism of action in this pathway, as PDE9 is significantly upregulated in patients with chronic heart failure, causing disruption in the beneficial NPS pathway that plays a protective role in cardiac function.
"Since the founding of Cardurion, our team has believed that the upregulation of PDE9 that occurs in heart failure is a critical element limiting the beneficial clinical effects of the highly validated NPS pathway," said Howard Surks, MD, Chief Medical and Scientific Officer of Cardurion.
Comprehensive Trial Design Addresses Both Heart Failure Types
The CYCLE clinical program consists of two complementary trials targeting different heart failure populations. CYCLE-1-REF (NCT06215911) enrolled approximately 560 patients with heart failure with reduced ejection fraction (HFrEF) and is evaluating three different doses of CRD-750 compared to placebo. CYCLE-2-PEF (NCT06215586) enrolled approximately 300 patients with heart failure with preserved ejection fraction (HFpEF) and is testing one dose of CRD-750 against placebo.
Both trials utilize N-terminal pro-B-type natriuretic peptide (NT-proBNP) as the primary endpoint, measuring changes in this cardiac biomarker that is released by the heart during heart failure. This endpoint has been previously validated in clinical trials of other approved heart failure therapies. Secondary endpoints include additional biomarkers and the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcomes scale.
Addressing Persistent Unmet Medical Need
Despite recent therapeutic advances, heart failure remains a condition with substantial morbidity and mortality. Approximately 50% of heart failure patients die within five years of diagnosis, and one in five patients are hospitalized annually, with 25% requiring readmission within a month of discharge. The condition affects roughly equal numbers of patients with reduced ejection fraction and preserved ejection fraction, categorized as different diseases based on the heart's pumping ability.
"Despite recent approvals, a large unmet medical need persists and patients with heart failure continue to experience high rates of morbidity and mortality," said James Udelson, MD, Chief of Cardiology at Tufts Medical Center and Principal Investigator for both CYCLE trials. "PDE9 inhibition is a promising new mechanism in the NPS pathway that may offer an opportunity to improve the standard of care treatment for the millions of patients with both types of chronic heart failure."
Clinical Development Milestone
The completion of enrollment represents a major advancement for Cardurion's clinical program, as the company becomes the first to demonstrate clinical proof-of-mechanism for PDE9 inhibition in patients with chronic heart failure. The company's pipeline also includes product candidates targeting calcium/calmodulin-dependent protein kinase II (CaMKII), representing another novel target for cardiovascular disease treatment.
Cardurion plans to present the Phase 2 results from these clinical trials at a future medical meeting, with the cardiovascular treatment community eagerly awaiting the outcomes of this innovative therapeutic approach.
