Adenosine Regulation with GP531 Improves the Heart’s Pumping Function in Dogs with Advanced Chronic Heart Failure
NEW YORK, June 3 /PRNewswire/ -- PeriCor Therapeutics, Inc. announced today that positive preclinical results of its novel cardioprotective agent, GP531, were reported in a poster presentation by Hani N. Sabbah, Ph.D., at the European Heart Failure Congress 2009 in Nice, France. The study was funded by PeriCor Therapeutics, Inc. and conducted by Dr. Sabbah and colleagues at the Division of Cardiovascular Medicine of the Henry Ford Health System, Detroit, Michigan. GP531 is an investigational drug under development by PeriCor Therapeutics under an Investigational New Drug (IND) application.
The study entitled “Intravenous GP531, an Adenosine Regulating Agent, Improves Left Ventricular Function in Dogs with Chronic Advanced Heart Failure” found that an acute intravenous infusion of GP531 at doses ranging from 3 mcg/kg/min to 300 mcg/kg/min significantly improves left ventricular (LV) systolic function. GP531 treatment, as compared to placebo, increased ejection fraction and decreased LV end-diastolic pressure, end-diastolic volume and end-systolic volume. This improvement in the heart’s pumping ability was achieved without increasing heart rate or lowering blood pressure, and GP531 did not elicit de-novo ventricular arrhythmias, even at the highest doses.
GP531 is a second generation member of a novel new class of cardioprotective compounds known as adenosine regulating agents (ARAs). ARAs, including GP531, have demonstrated impressive cardioprotective activity in preclinical models of ischemia/reperfusion injury, but this pilot study is the first to evaluate an ARA in a model of heart failure. Dr. Sabbah stated, “This encouraging preclinical study strongly supports continued preclinical and clinical exploration of GP531 as an adjunct therapy for the treatment of acute heart failure syndromes. GP531 represents a novel cardioprotective approach with a unique mechanism of action that addresses key functional maladaptations responsible for the worsening heart failure state.” “The beneficial effects of GP531 were remarkably consistent within this study,” noted David G. Shand, M.D., Ph.D., Senior Advisor for Clinical and Scientific Affairs. “The findings provide important insights for further evaluation of GP531 in heart failure.” Results from these studies should be reported later this year and early next year. Richard Stover, President and CEO of PeriCor Therapeutics, Inc., added, “We are confident that these studies will provide additional insights into this novel approach to improve global myocardial function in patients with heart failure, and we plan to initiate a Phase II study of GP531 in acute decompensated heart failure during the second half of the year.”
About GP531
GP531 is an adenosine regulating agent (ARA) that has been shown to amplify the body’s broad-spectrum protective response -- the localized release of endogenous adenosine -- during episodes of cellular stress. Cellular stress, as occurs with ischemia and tissue hypoxia, triggers the breakdown of adenosine triphosphate (ATP). ATP is the key energy molecule of living cells. Endogenous adenosine has been termed a “retaliatory metabolite” that targets multiple pathways of cellular stress and myocardial injury to counter net ATP catabolism and, as such, acts as a key regulator of cellular energetics. Endogenous adenosine protects cells from multiple pathways of injury such as inflammation, apoptosis and necrosis. Endogenous adenosine levels have been shown to be elevated in heart failure patients but not sufficiently to be cardioprotective.
By augmenting a patient’s own adenosine release in stressed tissues of the heart and its microvasculature, GP531 may have the potential to protect the heart muscle from further damage, alter the deterioration of cellular energetics, and improve global cardiac function. Importantly, ARAs’ effects are not mediated by conversion of the drug to adenosine or by any direct activity at the adenosine receptors. Rather, ARAs have been shown to increase endogenous adenosine release in an event-specific and site-specific fashion, remaining pharmacologically silent in the absence of net ATP breakdown.
About PeriCor Therapeutics
PeriCor Therapeutics, Inc. is a privately-held specialty biopharmaceutical company focused on the development and commercialization of a new class of medicines, adenosine regulating agents, to improve treatment and patient outcomes in acute-care settings of ischemia/reperfusion injury and heart failure. In August 2007, PeriCor granted worldwide development and commercialization rights for its first generation ARA, acadesine, to Schering-Plough Corporation under a licensing agreement. Last month, Schering-Plough announced the initiation of a Phase III pivotal trial of acadesine, an investigational drug, to reduce serious adverse cardiovascular outcomes associated with CABG surgery.
CONTACT: Richard R. Stover of PeriCor Therapeutics, Inc., +1-212-601-2725
