Novartis Entresto receives positive CHMP opinion for pediatric heart failure

Novartis announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of Entresto (sacubitril/valsartan) for a new indication to treat symptomatic chronic heart failure with left ventricular systolic dysfunction in pediatric patients aged from 1 to <18 years.

“Many children diagnosed with heart failure will need a heart transplant before they turn five or in the worst cases almost a third will die within a year. However, the disease is largely managed with treatments approved for adults, based on data from adult studies,” said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. “This positive opinion paves the way towards Novartis being able to provide children diagnosed with heart failure due to left ventricular systolic dysfunction in the EU and their families with an effective therapy in an age-appropriate formulation, helping to address what is a major unmet need.”

The positive opinion is based on final data from the 52-week Phase III PANORAMA-HF trial – the largest pediatric heart failure study ever conducted – and extrapolation of adult heart failure data from the Phase III PARADIGM-HF trial to pediatric patients. The data showed Entresto provided similar clinically meaningful reductions from baseline in the cardiac biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) – a biomarker commonly used to assess the severity and prognosis of heart failure – in adult heart failure patients and pediatric patients aged 1 to <18 years with heart failure due to left ventricular systolic dysfunction, allowing extrapolation of the demonstrated efficacy in adults to pediatric patients. Compared to enalapril, the current standard of care in pediatric heart failure (but not specifically approved for pediatric heart failure), Entresto provided comparable to numerically better improvements from baseline on a number of clinically relevant endpoints. Safety and tolerability of Entresto in pediatric patients were consistent with that observed in adult patients.

Pediatric heart failure represents an important cause of morbidity and mortality in childhood. Up to 33% of all pediatric cardiac admissions are related to heart failure, and children whose hospitalization is complicated by heart failure can have more than a 20-fold increase in the risk of death.

In this new indication the CHMP concluded that Entresto brings an important contribution to patient care and therefore fulfills the criteria of significant clinical benefit. If approved, Entresto will become available to children with a new age-appropriate formulation to enable accurate and convenient administration for these patients and their caregivers. This would support extension of the regulatory data protection to November 2026.

Entresto has been approved in the EU since 2015 in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF)⁴. In the US, Entresto is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, and has been approved since October 2019 to treat childhood heart failure due to left ventricular systolic dysfunction.