Serelaxin Safely Boosts Renal Perfusion in Small Chronic Heart Failure Study

September 24, 2013

ORLANDO, FL — The investigational drug serelaxin (Novartis Pharmaceuticals), a recombinant form of the hormone relaxin-2 that has been tested primarily in acute decompensated heart failure (ADHF) with promising results, appeared to significantly improve renal blood flow in a small study of patients with chronic, largely stable heart failure[1]. It had no apparent effect, in either direction, on glomerular filtration rate (GFR) and had a "placebolike" safety and tolerability profile, according to Dr Adriaan Voors (University of Groningen, the Netherlands).

Voors reported the randomized, placebo-controlled trial with 65 patients here at the Heart Failure Society of America 2013 Scientific Meeting . It follows the release of the substantially larger Relaxin for the Treatment of Acute Heart Failure (RELAX-AHF) trial, in which the agent alleviated dyspnea, reduced the risk of heart-failure exacerbations, and may have reduced all-cause and cardiovascular mortality at six months, as covered by heartwire .

In the chronic heart failure study, patients with NYHA class 2 or 3 heart failure who were stable on standard medications, including a loop diuretic, for at least a month, with an LVEF <45% and elevated natriuretic peptides, were randomized to receive serelaxin as a 24-hour IV infusion (30 µg/kg over 24 hours) or placebo.

Compared with the 37 control patients, the 28 who received serelaxin showed a 16% rise in renal plasma flow (p=0.004) during the 24-hour infusion, a 13% rise from hour 8 to hour 24 (p=0.039), and a 16% jump from hour 24 to hour 28 (p=0.011). GFR at those intervals had neither risen nor fallen significantly. Nor were there significant differences between groups in changes in systolic blood pressure, creatinine clearance, or sodium excretion. Reductions in diastolic blood pressure reached significance compared with placebo only at hour 4 and hour 8.

As discussant following Voors' presentation, Dr John C Burnett Jr (Mayo Clinic, Rochester, MN) said serelaxin has been an "exciting" drug for its performance in ADHF, an area that has seen very few new effective agents over the years, but its exploration in chronic heart failure has only started.

In the current study, "the increase in renal blood flow was reassuring," said Burnett, an expert in the neuroendocrine system as it relates to the heart and kidneys. Oxygen delivery to the kidneys is impaired in chronic heart failure, "and I'm sure in acute heart failure, even more so. If we can present more oxygen to the kidney, we can protect it structurally as well as functionally, especially the hard-working tubules."

Even more reassuring, he said, would have been if the increased renal perfusion had manifested as improved GFR or sodium excretion.

Voors had no disclosures. Burnett is chair of SAB Nile Therapeutics, cofounder of Anexon, cofounder of Zumbro Discovery, and a consultant for Bayer, AstraZeneca, Novartis, and Merck.

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