Date: 2012-08-26
Type of information: Publication of results in a medical journal
phase: 2
Announcement: results and publication in the Lancet ( Solomon S, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. www.thelancet.com. Published online August 26, 2012 http://dx.doi.org/10.1016/S0140-6736(12)61227-6.)
Company: Novartis (Switzerland)
Product: LCZ696
Action
mechanism: LCZ696 is the first in a new class of medicines called angiotensin receptor neprilysin inhibitors (ARNIs). It works in a different way to existing heart failure treatments 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 therefore acts simultaneously on two important pathways in the development of the disease.
Disease: heart failure with preserved ejection fraction (HF-PEF)
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: PARAMOUNT was an international 36-week, randomized, double-blind, multicenter, parallel group, active-controlled study to compare the efficacy, safety, and tolerability profile of LCZ696 with valsartan in patients with HF-PEF. The study consisted of a 12-week core study and a 24-week extension phase. The study included 301 patients (mean age 71 years) with HF-PEF (left ventricular ejection fraction >45%). They all had elevated NT-proBNP (>400 pg/ml) and at least one of the following symptoms of HF-PEF: shortness of breath on exertion, shortness of breath when lying flat, episodes of 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 one week and doubled again after a further week to a maximum dose of 200 mg and 160 mg twice-daily, respectively.
Latest
news: Novartis has announced results from the Phase II PARAMOUNT study showing that the investigational compound LCZ696 is the first therapy to significantly reduce a key predictor of morbidity and mortality in patients with a condition called heart failure with preserved ejection fraction (HF-PEF). The data were presented at the ESC Congress 2012 (European Society of Cardiology) in Munich, Germany, and published simultaneously in The Lancet.
The results show that after 12 weeks, LCZ696 met its primary endpoint by reducing NT-proBNP (N-terminal pro-B-type natriuretic peptide - 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 patients with heart failure.
The PARAMOUNT study showed that after 12 weeks of treatment, reduction in NT-proBNP was 23% greater with LCZ696 than valsartan (p=0.005). In addition, there was a greater reduction (p=0.003) in left atrial size (cardiac remodeling) in LCZ696-treated patients at the end of the 36-week study. This suggests that LCZ696 could provide an effective treatment for patients with HF-PEF. The study also showed that LCZ696 had an acceptable safety profile and was well tolerated in patients with HF-PEF.
