Novartis has announced results from the Phase II PARAMOUNT study showing that the investigational compound LCZ696 significantly reduces a key predictor of morbidity and mortality in patients with heart failure with preserved ejection fraction (HF-PEF). The results show that after 12 weeks, LCZ696 met its primary endpoint by reducing N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of stress on the heart and a predictor of patient outcomes, significantly more than valsartan. The data also suggest that LCZ696 may reverse some structural changes to the heart that occur in heart failure patients.
LCZ696 is the first in a new class of medicines called angiotensin receptor neprilysin inhibitors (ARNIs). It works by inhibiting an enzyme (neprilysin, or NEP) in order to promote the body's protective mechanisms and blocking receptors involved in the narrowing of blood vessels (angiotensin receptors). LCZ696 acts simultaneously on two important pathways in the development of the disease.
PARAMOUNT was a 36-week, randomized, double-blind, active-controlled study that compared the efficacy, safety, and tolerability profile of LCZ696 with valsartan in patients with HF-PEF. Consisting of a 12-week core study and a 24-week extension phase, it included 301 patients with HF-PEF. They all had elevated NT-proBNP and at least one of these symptoms of HF-PEF: shortness of breath on exertion, shortness of breath when lying flat, shortness of breath at night, and swollen ankles. After stopping any treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), they were randomized to LCZ696 (50 mg twice daily) or valsartan (40 mg twice daily), an ARB indicated for heart failure. Doses of both drugs were doubled after a week and again after another week to a maximum dose of 200 mg and 160 mg twice daily, respectively. Read a summary of the findings, as they appeared in The Lancet.