Preclinical studies of Cardioxyl’s HNO prodrugs demonstrate effective treatment of chronic diastolic dysfunction and potential for oral administration
Researchers testing Cardioxyl Pharmaceuticals, Inc. experimental HNO prodrugs presented data demonstrating that HNO improves cardiac function in animal models of diastolic heart failure, and separately that an orally administered HNO prodrug produces the same attractive hemodynamic improvements previously demonstrated with intravenous infusion. Data from studies conducted by scientists at QTest Labs, Cardioxyl, MPI Research Inc. and Ohio State University were presented at the American Heart Association Scientific Sessions 2014 in Chicago.
Key findings from the presentations include:
- Experimental HNO prodrug CXL-1020 improved ventricular relaxation and systolic function in two different preclinical models of chronic diastolic dysfunction, a disease that has so far eluded effective clinical therapy. HNO also compared favorably in key hemodynamic parameters against the cAMP dependent therapy Milrinone.
- Oral dosages of another experimental HNO prodrug, CXL-1036, produced enhanced inotropy (systolic pump function), lusitropy (diastolic relaxation) and vasodilation while decreasing cardiac energy demand in animal models. The magnitude of hemodynamic effects following oral administration of this HNO prodrug were equivalent to those observed following intravenous delivery and no diminution of activity (tachyphylaxis) was observed with repeat dosing. The demonstration of orally active HNO prodrugs creates an opportunity to explore the utility of HNO in treating heart failure in an outpatient setting.
“We are very excited about these findings, which suggest that HNO prodrugs could be useful in the treatment of diastolic heart failure,” said John Reardon, Ph.D., Cardioxyl’s Chief Scientific Officer. “In addition, the demonstration of oral effectiveness in animal models could pave the way for the use of HNO prodrugs in the outpatient therapy of both systolic and diastolic heart failure.”
About Cardioxyl’s HNO Prodrug Candidates
CXL-1036 and CXL-1020, like other experimental compounds under development at Cardioxyl, are prodrugs that release HNO in the bloodstream following administration. Nitroxyl, the chemical name for HNO, has been studied for its potential as a treatment for heart failure; it acts to dilate blood vessels and works directly on the heart through a unique mechanism to enhance both systolic and diastolic cardiac function. Cardioxyl’s proprietary platform of HNO technology has produced a number of candidate therapeutics for treating heart failure, the most advanced of which is in a Phase II study.
HNO has been shown to produce a unique and very attractive combination of hemodynamic effects in both animal models and humans. This hemodynamic profile, comprised of improved contractility, lusitropy and vasodilation, distinguishes HNO prodrugs from other therapies used in the treatment of congestive heart failure and provides a strong rationale for the continuing development of this important new class of drugs.
Source: Cardioxyl Pharmaceuticals