The Food and Drug Administration (FDA) has approved Entresto (sacubitril/valsartan; Novartis) for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged 1 year and older.
The approval was based on data from the PANORAMA-HF trial, a double-blind study that compared the effectiveness and safety of Entresto with enalapril in pediatric patients 1 to <18 years old with heart failure (NYHA/Ross Class II-IV) due to systemic left ventricular systolic dysfunction (LVEF ≤40%) (N=110). The primary end point of the study was the between-group difference in the change in plasma NT-proBNP from baseline to Week 12.
Results showed that the reduction from baseline in NT-proBNP was 44% in the Entresto group compared with 33% in the enalapril group. While not statistically significant, the reductions were similar or larger than what were seen in adult patients. As such, this effect on NT-proBNP was considered a reasonable basis to infer improved cardiovascular outcomes in the pediatric population, as similar outcomes were observed in the PARADIGM-HF study.
With regard to safety, adverse reactions observed in pediatric patients treated with Entresto were consistent with those observed in adult patients. These included hypotension, hyperkalemia, cough, dizziness, and renal failure.
“The current clinical management of pediatric systolic heart failure includes the use of several medicines based mostly on data from adult studies, and there is limited data in children with heart failure in clinical trials,” said David Soergel, MD, Global Head of Cardiovascular, Renal and Metabolic Drug Development at Novartis. “PANORAMA-HF is ongoing to secure 52-week follow-up data for the full study population. We remain committed to trial completion to generate further evidence on how Entresto impacts the clinical course of pediatric HF.”
Entresto, which combines a neprilysin inhibitor and an angiotensin II receptor blocker (ARB), is also indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It is supplied as 24mg/26mg, 49mg/51mg, and 97mg/103mg strength tablets. An oral suspension formulation can be substituted at the recommended tablet dosage in patients unable to swallow tablets. Instructions on how to prepare the oral suspension can be found here.
For more information visit novartis.com.