US-based Cardurion Pharmaceuticals has completed enrolment in two multi-centre, global Phase II CYCLE trials of the orally-administered phosphodiesterase 9 (PDE9) inhibitor, CRD-750, targeting both chronic heart failure (HF) types- HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).
The CYCLE-1-REF study has included nearly 560 HF subjects with HFrEF, testing three doses of the therapy against a placebo.
The CYCLE-2-PEF trial enrolled approximately 300 HF subjects with HFpEF to assess a single dose of the therapy against a placebo.
The change in N-terminal pro B-type natriuretic peptide is the primary goal for both trials.
NT-proBNP minimisation is a biomarker used in trials for other approved HF therapies. Alongside this primary endpoint, the trials will assess secondary endpoints, including the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcomes scale, and additional biomarkers.
Cardurion Pharmaceuticals' chief medical and scientific officer Howard Surks said: “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. Our progress brings us closer to our goal of leveraging PDE9 inhibition to address unmet needs for patients.
“We look forward to receiving the Phase II results from these clinical trials and presenting them at a future medical meeting.”
CRD-750 is said to be a new approach to improving the natriuretic peptide signalling (NPS) pathway, which is significant for treating HF patients.
PDE9 is an enzyme which, when overactive in HF patients, disrupts the beneficial effects of the NPS pathway.
Cardurion's CRD-750 aims to counteract this disruption, as PDE9 is upregulated in individuals with chronic HF.
The company's pipeline also includes product candidates that target calcium/calmodulin-dependent protein kinase II (CaMKII).
Last year, Cardurion secured $260m in Series B funding to progress its cardiovascular drug pipeline.
